Giardia duodenalis: Flavohemoglobin is involved in drug biotransformation and resistance to albendazole.

Giardia duodenalis causes giardiasis, a major diarrheal disease in humans worldwide whose treatment relies mainly on metronidazole (MTZ) and albendazole (ABZ). The emergence of ABZ resistance in this parasite has prompted studies to elucidate the molecular mechanisms underlying this phenomenon. G. duodenalis trophozoites convert ABZ into its sulfoxide (ABZSO) and sulfone (ABZSOO) forms, despite lacking canonical enzymes involved in these processes, such as cytochrome P450s (CYP450s) and flavin-containing monooxygenases (FMOs). This study aims to identify the enzyme responsible for ABZ metabolism and its role in ABZ resistance in G. duodenalis. We first determined that the iron-containing cofactor heme induces higher mRNA expression levels of flavohemoglobin (gFlHb) in Giardia trophozoites. Molecular docking analyses predict favorable interactions of gFlHb with ABZ, ABZSO and ABZSOO. Spectral analyses of recombinant gFlHb in the presence of ABZ, ABZSO and ABZSOO showed high affinities for each of these compounds with Kd values of 22.7, 19.1 and 23.8 nM respectively. ABZ and ABZSO enhanced gFlHb NADH oxidase activity (turnover number 14.5 min-1), whereas LC-MS/MS analyses of the reaction products showed that gFlHb slowly oxygenates ABZ into ABZSO at a much lower rate (turnover number 0.01 min-1). Further spectroscopic analyses showed that ABZ is indirectly oxidized to ABZSO by superoxide generated from the NADH oxidase activity of gFlHb. In a similar manner, the superoxide-generating enzyme xanthine oxidase was able to produce ABZSO in the presence of xanthine and ABZ. Interestingly, we find that gFlHb mRNA expression is lower in albendazole-resistant clones compared to those that are sensitive to this drug. Furthermore, all albendazole-resistant clones transfected to overexpress gFlHb displayed higher susceptibility to the drug than the parent clones. Collectively these findings indicate a role for gFlHb in ABZ conversion to its sulfoxide and that gFlHb down-regulation acts as a passive pharmacokinetic mechanism of resistance in this parasite.

Use of overnight metyrapone test in suspected secondary adrenal insufficiency: A retrospective single centre-study.

OBJECTIVE: Overnight metyrapone test (OMT) is a dynamic test used to diagnose secondary adrenal insufficiency (SAI). Data on OMT use and its safety are scarce. We aimed to describe the indications and safety of outpatient OMT and compare OMT to the cosyntropin stimulation test (CST). DESIGN: Single-centre retrospective study of adult patients undergoing OMT between 1 April 2018 and 27 January 2023. MEASUREMENTS: OMT-related adverse events, post-OMT diagnosis of SAI, and OMT comparison to CST. RESULTS: OMT was performed in 114 patients (81, 71% women) at a median age of 48 (interquartile range 37-58). The pretest probability for SAI was low in 52 (46%) patients, moderate in 48 (42%) patients and high in 14 (12%) patients. Adverse events were reported in 7 (6.1%) patients and were mild except for one hospitalization. No baseline or OMT-related factors were associated with the development of adverse events. Prevalence of the OMT-based SAI diagnosis was 26 (23%) and 47 (46%) using 11-deoxycortisol cutoff <7 and <10 mcg/dL, respectively. Higher pretest probability was associated with the OMT-based diagnosis of SAI. Post-OMT 11-deoxycortisol cutoff of 10 mcg/dL was used most to diagnose SAI. Compared to the OMT-based diagnosis of SAI (11-deoxycortisol cutoff of 10 mcg/dL), the specificity of CST was 100%, but the sensitivity was only 52%. CONCLUSIONS: OMT was well tolerated and used in patients with low and moderate pretest probability for SAI. CST can erroneously exclude patients with SAI. Thus, OMT should be considered in selected patients with normal CST.

Active chiral dynamics and boundary accumulation phenomenon in confined camphor particles.

In this work, we perform experimental and numerical investigations on the dynamics of camphor-infused discs, well-established as active particles in their behavior. Our analysis focuses on examining the individual dynamics of these discs within a confined circular domain, revealing that they exhibit characteristics akin to active chiral particles. To characterize this behavior effectively, we introduce a methodology for estimating key model parameter values from our experiments, including linear velocity, angular velocity, and angular noise intensity. To validate our findings, we compare our experimental results with numerical simulations of the model. Our results demonstrate a striking phenomenon associated with camphor-infused discs: a pronounced accumulation of particles along the boundary. This intriguing observation suggests the occurrence of an attractive interaction between the active particles and the boundary, resulting in a kind of adsorption effect. The latter results in the confinement of the camphor disc along the Petri dish wall, which we refer to as sliding dynamics. We empirically determine the velocity of the particle along the Petri dish wall as well as its fluctuations, properties whose behavior notably deviates from the bulk dynamics.

In Vivo, In Vitro and In Silico Anticancer Activity of Ilama Leaves: An Edible and Medicinal Plant in Mexico.

Ilama leaves are an important source of secondary metabolites with promising anticancer properties. Cancer is a disease that affects a great number of people worldwide. This work aimed to investigate the in vivo, in vitro and in silico anticancer properties of three acyclic terpenoids (geranylgeraniol, phytol and farnesyl acetate) isolated from petroleum ether extract of ilama leaves. Their cytotoxic activity against U-937 cells was assessed using flow cytometry to determine the type of cell death and production of reactive oxygen species (ROS). Also, a morphological analysis of the lymph nodes and a molecular docking study using three proteins related with cancer as targets, namely, Bcl-2, Mcl-1 and VEGFR-2, were performed. The flow cytometry and histomorphological analysis revealed that geranylgeraniol, phytol and farnesyl acetate induced the death of U-937 cells by late apoptosis and necrosis. Geranylgeraniol and phytol induced a significant increase in ROS production. The molecular docking studies showed that geranylgeraniol had more affinity for Bcl-2 and VEGFR-2. In the case of farnesyl acetate, it showed the best affinity for Mcl-1. This study provides information that supports the anticancer potential of geranylgeraniol, phytol and farnesyl acetate as compounds for the treatment of cancer, particularly with the potential to treat non-Hodgkin's lymphoma.

Pneumatosis coli, a rare cause of chronic abdominal pain.

Pneumatosis coli is a rare entity, characterised by the formation of intramural air cysts in the colonic wall. Diagnosis can be made by CT and colonoscopy, which may suggest this aetiology. We present the case of a 51-year-old patient who consulted for abdominal pain and diarrhoea and underwent colonoscopy with findings of multiple lesions between 5-10 mm with polypoid morphology and submucosal appearance in the transverse colon and splenic angle. Given the suspicion of pneumatosis, these lesions were punctured with a 3-mm injection needle and then aspirated with a syringe, extracting gas and observing the collapse of the lesions. This confirms the diagnosis of pneumatosis coli, also improving the patient's clinical condition. This case shows the importance of endoscopic imaging, as well as the fact that injection needle aspiration allows the diagnosis of coli pneumatosis, being a safe and effective method that does not require other diagnostic tests.

[Prescription of drugs for smoking cessation. Retrospective analysis of the health area of Zamora]. / Prescripción de fármacos para la deshabituación tabáquica. Análisis retrospectivo del área de salud de Zamora.

OBJECTIVE: To analyze the prescription of drugs to aid smoking cessation and to detect whether there are differences by age or sex. DESIGN: Retrospective cohort study. SITE: Zamora Health Area. PARTICIPANTS: Persons with smoking cessation attempts employing drugs funded in the period from 2020 to 2023. INTERVENTIONS: Request of pharmaceutical consumption of varenicline, bupropion and cytisine to the Pharmacy Information System of the Regional Health Management of Castilla y León. MAIN MEASUREMENTS: Number of quit attempts per person, treatment drug, number of medication containers per attempt, year, age and sex. Descriptive and statistical analysis using SPSS© v. 20. RESULTS: 2581 people tried to quit smoking with drugs, 2206 made one attempt and 375 made several attempts. Mean age was 50.7 years (95% CI: 50.2-51.1). No significant differences were found for age (P=.71) or sex (P=.74). There was a preference for prescribing varenicline over bupropion and low drug compliance, with only one container of medication being collected in about 50% of cases. A total of 1680 attempts were made to quit using cytisine in 2023, equivalent to 55.4% of the total number of treatment drugs used in the four years. The estimated cumulative incidence rate of drug withdrawal attempts in smokers between 18 and 65 years of age was 11.9%. CONCLUSIONS: The drug intervention had a low reach and poor compliance with the recommended treatment. It is essential to emphasize patient follow-up and drug adherence.

Preconception Periodontitis and Risk of Spontaneous Abortion in a Prospective Cohort Study.

Few studies have evaluated the association between periodontitis and spontaneous abortion (SAB), and all had limitations. We used data from the Pregnancy Study Online (PRESTO), a prospective preconception cohort study of 3,444 pregnancy planners in the United States and Canada (2019-2022), to address this question. Participants provided self-reported data on periodontitis diagnosis, treatment, and symptoms of severity (i.e., loose teeth) via the enrollment questionnaire. SAB (pregnancy loss at <20 weeks' gestation) was assessed via bimonthly follow-up questionnaires. Participants contributed person-time from the date of a positive pregnancy test to the gestational week of SAB, loss to follow-up, or 20 weeks' gestation, whichever came first. We fitted Cox regression models with weeks of gestation as the time scale to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs), and we used inverse probability of treatment weighting to account for differential loss to follow-up. We used probabilistic quantitative bias analysis to estimate the magnitude and direction of the effect of exposure misclassification bias on results. In weighted multivariable models, we saw no appreciable association between preconception periodontitis diagnosis (HR = 0.97, 95% CI: 0.76, 1.23) or treatment (HR = 1.01, 95% CI: 0.79, 1.27) and SAB. A history of loose teeth was positively associated with SAB (HR = 1.38, 95% CI: 0.88, 2.14). Quantitative bias analysis indicated that our findings were biased towards the null but with considerable uncertainty in the bias-adjusted results.

Childhood adversities and mental disorders in first-year college students: results from the World Mental Health International College Student Initiative.

BACKGROUND: This study investigates associations of several dimensions of childhood adversities (CAs) with lifetime mental disorders, 12-month disorder persistence, and impairment among incoming college students. METHODS: Data come from the World Mental Health International College Student Initiative (WMH-ICS). Web-based surveys conducted in nine countries (n = 20 427) assessed lifetime and 12-month mental disorders, 12-month role impairment, and seven types of CAs occurring before the age of 18: parental psychopathology, emotional, physical, and sexual abuse, neglect, bullying victimization, and dating violence. Poisson regressions estimated associations using three dimensions of CA exposure: type, number, and frequency. RESULTS: Overall, 75.8% of students reported exposure to at least one CA. In multivariate regression models, lifetime onset and 12-month mood, anxiety, and substance use disorders were all associated with either the type, number, or frequency of CAs. In contrast, none of these associations was significant when predicting disorder persistence. Of the three CA dimensions examined, only frequency was associated with severe role impairment among students with 12-month disorders. Population-attributable risk simulations suggest that 18.7-57.5% of 12-month disorders and 16.3% of severe role impairment among those with disorders were associated with these CAs. CONCLUSION: CAs are associated with an elevated risk of onset and impairment among 12-month cases of diverse mental disorders but are not involved in disorder persistence. Future research on the associations of CAs with psychopathology should include fine-grained assessments of CA exposure and attempt to trace out modifiable intervention targets linked to mechanisms of associations with lifetime psychopathology and burden of 12-month mental disorders.

Periodontitis is associated with an increased hazard of mortality in a longitudinal cohort study over 50 years.

AIM: To evaluate the association between periodontal disease and all-cause mortality in a longitudinal cohort study over 50 years. MATERIALS AND METHODS: Participants (N = 1156) in the Veterans Affairs Dental Longitudinal Study, aged 25-85 years at enrollment in 1968, received comprehensive medical and oral exams approximately every 3 years through 2007. Periodontal status was defined using person-level, mean whole-mouth radiographic alveolar bone loss (ABL) scores using a five-point Schei ruler, each unit representing 20% increments of ABL. Time-varying Cox regression models estimated hazard ratios (HRs) for the association between continuous and categorical ABL and mortality, adjusting for covariates. RESULTS: Each one-unit increase in mean ABL score was associated with a 14% increase in the hazard of mortality (adjusted HR = 1.14, 95% confidence interval [CI] 1.02, 1.27). When assessed categorically, HRs for average scores of 2 to <3 and 3 to ≤5 showed increasing associations with hazard of mortality, relative to 0 to <1 (adjusted HR = 1.17, 95% CI 0.94, 1.46; and HR = 1.65, 95% CI 0.94, 2.85, respectively). By contrast, we observed null associations for average scores of 1 to <2 relative to 0 to <1 (adjusted HR = 1.00, 95% CI 0.86, 1.17). CONCLUSIONS: Time-varying periodontal status assessed using radiographic ABL was positively associated with all-cause mortality even after confounder adjustment.

A longitudinal study on the impact of Internet gaming disorder on self-perceived health, academic performance, and social life of first-year college students.

BACKGROUND AND OBJECTIVES: Internet gaming disorder (IGD) is associated with health, social, and academic problems but whether these are consequences of the disorder rather than precursors or correlates is unclear. We aimed to evaluate whether IGD in the 1st year of university predicts health, academic and social problems 1 year later, controlling for baseline health, academic and social problems, demographics, and mental health symptoms. METHODS: In a prospective cohort study, 1741 university students completed both a baseline online survey in their 1st year and a follow-up survey 1 year later. Log-binomial models examined the strength of prospective associations between baseline predictor variables (IGD, baseline health, academic and social problems, sex, age, and mental health symptoms) and occurrence of health, academic and social problems at follow-up. RESULTS: When extensively adjusted by the corresponding outcome at baseline, any mental disorder symptoms, sex, and age, baseline IGD was associated only with severe school impairment and poor social life (risk ratio [RR] = 1.77; 95% confidence interval [CI] = 1.14-2.75, p = .011; RR = 1.22; 95% CI = 1.07-1.38, p = .002, respectively). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: University authorities and counselors should consider that incoming 1st-year students that meet criteria for IGD are likely to have increased academic and social impairments during their 1st year for which they may want to intervene. This study adds to the existing literature by longitudinally examining a greater array of negative outcomes of IGD than previously documented.

Recruitment and Enrollment of Low-income, Minority Residents of Urban Public Housing into Research.

Research participation among vulnerable populations is often limited by the same socioeconomic factors that contribute to poor health. Identifying best practices for inclusion is critical to addressing health disparities. Urban public housing communities bear a disproportionate burden of chronic disease and may represent an opportunity to directly engage historically vulnerable populations in research designed to ultimately reduce that burden. We used mixed-method data to analyze recruitment effectiveness among a random sample of households (N = 380) across two public housing developments in Boston, MA who were approached for participation in a pre-COVID oral health study. Quantitative data from detailed recruitment tracking methods was analyzed to assess the relative efficiency of the methods employed. Field journals of study staff were qualitatively analyzed to identify community-specific recruitment barriers and facilitators. The participation rate among randomly sampled households was 28.6% (N = 131), with participation from primarily Hispanic (59.5%) or Black (26%) residents. Door-to-door knocking with response yielded the highest participation (44.8%), followed by responses to informational study flyers (31%). Primary barriers to enrollment included references to unemployment and employment variations, shift work, childcare responsibilities, time demands, and managing multiple appointments and social services. This study finds active, door-to-door knocking and return visits resolved barriers to participation, and reduced safety concerns and historic distrust. It's time to consider how best to adapt effective pre-COVID recruitment practices for utilization under current and future exposure conditions as effective recruitment of populations such as urban public housing residents into research is only becoming more important.

Microwave Resonators for Wearable Sensors Design: A Systematic Review.

The field of flexible electronics is undergoing an exponential evolution due to the demand of the industry for wearable devices, wireless communication devices and networks, healthcare sensing devices and the technology around the Internet of Things (IoT) framework. E-tex tiles are attracting attention from within the healthcare areas, amongst others, for providing the possibility of developing continuous patient monitoring solutions and customized devices to accommodate each patient's specific needs. This review paper summarizes multiple approaches investigated in the literature for wearable/flexible resonators working as antenna-based systems, sensors and filters with special attention paid to the integration to flexible materials, especially textiles. This review manuscript provides a general overview of the flexible resonators' advantages and drawbacks, materials, fabrication techniques and processes and applications. Finally, the main challenges and future prospects of wearable resonators are discussed.

Wearable Sensors for Respiration Monitoring: A Review.

This paper provides an overview of flexible and wearable respiration sensors with emphasis on their significance in healthcare applications. The paper classifies these sensors based on their operating frequency distinguishing between high-frequency sensors, which operate above 10 MHz, and low-frequency sensors, which operate below this level. The operating principles of breathing sensors as well as the materials and fabrication techniques employed in their design are addressed. The existing research highlights the need for robust and flexible materials to enable the development of reliable and comfortable sensors. Finally, the paper presents potential research directions and proposes research challenges in the field of flexible and wearable respiration sensors. By identifying emerging trends and gaps in knowledge, this review can encourage further advancements and innovation in the rapidly evolving domain of flexible and wearable sensors.

Textile Antenna Sensor in SIW Technology for Liquid Characterization.

This study showcases the creation of an innovative textile antenna sensor that utilizes a resonant cavity for the purpose of liquid characterization. The cavity is based on circular substrate integrated waveguide (SIW) technology. A hole is created in the middle of the structure where a pipe is used to inject the liquid under test. The pipe is covered by a metal sheath to enhance the electromagnetic field's penetration of the tube, thus increasing the device's sensitivity. The resonance frequency of the proposed system is altered when the liquid under test is inserted into the sensitive area of the structure. The sensing of the liquid is achieved by the measurement of its dielectric properties via the perturbation of the electric fields in the SIW configuration. The S11 measurement enables the extraction of the electromagnetic properties of the liquid injected into the pipe. Specifically, the dielectric constant of the liquid is determined by observing the resonance frequency shift relative to that of an air-filled pipe. The loss tangent of the liquid is extracted by comparing the variation in the quality factor with that of an air-filled pipe after eliminating the inherent losses of the structure. The proposed SIW antenna sensor demonstrates a high sensitivity of 0.7 GHz/Δεr corresponding to a dielectric constant range from 4 to 72. To the best of our knowledge, this article presents for the first time the ability of a fully textile SIW cavity antenna-based sensor to characterize the dielectric properties of a liquid under test and emphasizes its differentiating features compared to PCB-based designs. The unique attributes of the textile-based antenna stem from its flexibility, conformability, and compatibility with various liquids.

Extracellular Cysteine Proteases of Key Intestinal Protozoan Pathogens-Factors Linked to Virulence and Pathogenicity.

Intestinal diseases caused by protistan parasites of the genera Giardia (giardiasis), Entamoeba (amoebiasis), Cryptosporidium (cryptosporidiosis) and Blastocystis (blastocystosis) represent a major burden in human and animal populations worldwide due to the severity of diarrhea and/or inflammation in susceptible hosts. These pathogens interact with epithelial cells, promoting increased paracellular permeability and enterocyte cell death (mainly apoptosis), which precede physiological and immunological disorders. Some cell-surface-anchored and molecules secreted from these parasites function as virulence markers, of which peptide hydrolases, particularly cysteine proteases (CPs), are abundant and have versatile lytic activities. Upon secretion, CPs can affect host tissues and immune responses beyond the site of parasite colonization, thereby increasing the pathogens' virulence. The four intestinal protists considered here are known to secrete predominantly clan A (C1- and C2-type) CPs, some of which have been characterized. CPs of Giardia duodenalis (e.g., Giardipain-1) and Entamoeba histolytica (EhCPs 1-6 and EhCP112) degrade mucin and villin, cause damage to intercellular junction proteins, induce apoptosis in epithelial cells and degrade immunoglobulins, cytokines and defensins. In Cryptosporidium, five Cryptopains are encoded in its genome, but only Cryptopains 4 and 5 are likely secreted. In Blastocystis sp., a legumain-activated CP, called Blastopain-1, and legumain itself have been detected in the extracellular medium, and the former has similar adverse effects on epithelial integrity and enterocyte survival. Due to their different functions, these enzymes could represent novel drug targets. Indeed, some promising results with CP inhibitors, such as vinyl sulfones (K11777 and WRR605), the garlic derivative, allicin, and purified amoebic CPs have been obtained in experimental models, suggesting that these enzymes might be useful drug targets.

Use of Cells, Supplements, and Peptides as Therapeutic Strategies for Modulating Inflammation after Spinal Cord Injury: An Update.

Spinal cord injury is a traumatic lesion that causes a catastrophic condition in patients, resulting in neuronal deficit and loss of motor and sensory function. That loss is caused by secondary injury events following mechanical damage, which results in cell death. One of the most important events is inflammation, which activates molecules like proinflammatory cytokines (IL-1ß, IFN-γ, and TNF-α) that provoke a toxic environment, inhibiting axonal growth and exacerbating CNS damage. As there is no effective treatment, one of the developed therapies is neuroprotection of the tissue to preserve healthy tissue. Among the strategies that have been developed are the use of cell therapy, the use of peptides, and molecules or supplements that have been shown to favor an anti-inflammatory environment that helps to preserve tissue and cells at the site of injury, thus favoring axonal growth and improved locomotor function. In this review, we will explain some of these strategies used in different animal models of spinal cord injury, their activity as modulators of the immune system, and the benefits they have shown.

Payment Methods and Demographics Influence Patterns of Dental Service Utilization.

OBJECTIVE: To describe the patterns of specific dental service utilization among the various sociodemographic groups in North Carolina served by the East Carolina University School of Dental Medicine (ECU SoDM). DESIGN: This was a descriptive study utilizing self-reported patients' sociodemographic information, payment method history, and CDT codes of procedures performed. Deidentified clinical data recorded for 26 710 patients and 534 983 procedures from 2011 to 2020 were extracted from a centralized axiUm database. Data were analyzed using IBM SPSS Statistics, version 25.0. Cross-tabulations between dental service utilizations, patients' demographics, and payment method were performed using chi-square analysis. SETTING: Nine dental clinic sites across the state of North Carolina. PARTICIPANTS: In total, 26 710 adults 23 years to older than 65 years were included in the sample for this study. MAIN OUTCOME MEASURES: In total, 534 983 procedure codes completed for the eligible patients were cross-tabulated with payment method. RESULTS: Payment method was significantly related to individual characteristics including location of service, age, race, ethnicity, and untreated decay ( P < .001). Payment method is associated with the dental service type utilized by an individual ( P < .001). Patients who received Medicaid benefits were more likely to receive restorative procedures, removable prosthetics, or oral surgery. Despite NC Medicaid covering preventive procedures, patients who received Medicaid benefits showed lower utilization of preventive procedures than expected. Privately insured or self-paying individuals demonstrated a greater variety of service option utilization, as well as more frequent usage of more specialized procedure options such as endodontics, periodontics, fixed prosthodontics, and implants. CONCLUSIONS: Payment method was found to be related to patients' demographics and type of dental service utilized. Adults older than 65 years demonstrated a higher proportion of self-payment for dental care, indicating a lack of payment options for this population. In the interest of providing care for underserved populations in North Carolina, policy makers should consider expanding dental coverage for adults older than 65 years.

Use of primary bariatric surgery among patients with obesity and diabetes. Insights from the Diabetes Collaborative Registry.

Despite its cardiometabolic benefits, bariatric surgery has historically been underused in patients with obesity and diabetes, but contemporary data are lacking. Among 1,520,182 patients evaluated from 2013 to 2019 within a multicenter, longitudinal, US registry of outpatients with diabetes, we found that 462,033 (30%) met eligibility for bariatric surgery. After a median follow-up of 854 days, 6310/384,859 patients (1.6%) underwent primary bariatric surgery, with a slight increase over time (0.38% per year [2013] to 0.68% per year [2018]). Patients who underwent bariatric surgery were more likely to be female (63% vs. 56%), white (87% vs. 82%), have higher body mass indices (42.1 ± 6.9 vs. 40.6 ± 5.9 kg/m2), and depression (23% vs. 14%; p < 0.001 for all). Over a median (IQR) follow-up after surgery of 722 days (364-993), patients who underwent bariatric surgery had lost an average of 11.8 ± 18.5 kg (23% of excess body weight), 10.2% were on fewer glucose-lowering medications, and 8.4% were on fewer antihypertensives. Despite bariatric surgery being safer and more accessible over the past two decades, less than one in fifty eligible patients with diabetes receive this therapy.

Poacic acid, a ß-1,3-glucan-binding antifungal agent, inhibits cell-wall remodeling and activates transcriptional responses regulated by the cell-wall integrity and high-osmolarity glycerol pathways in yeast.

As a result of the relatively few available antifungals and the increasing frequency of resistance to them, the development of novel antifungals is increasingly important. The plant natural product poacic acid (PA) inhibits ß-1,3-glucan synthesis in Saccharomyces cerevisiae and has antifungal activity against a wide range of plant pathogens. However, the mode of action of PA is unclear. Here, we reveal that PA specifically binds to ß-1,3-glucan, its affinity for which is ~30-fold that for chitin. Besides its effect on ß-1,3-glucan synthase activity, PA inhibited the yeast glucan-elongating activity of Gas1 and Gas2 and the chitin-glucan transglycosylase activity of Crh1. Regarding the cellular response to PA, transcriptional co-regulation was mediated by parallel activation of the cell-wall integrity (CWI) and high-osmolarity glycerol signaling pathways. Despite targeting ß-1,3-glucan remodeling, the transcriptional profiles and regulatory circuits activated by caspofungin, zymolyase, and PA differed, indicating that their effects on CWI have different mechanisms. The effects of PA on the growth of yeast strains indicated that it has a mode of action distinct from that of echinocandins, suggesting it is a unique antifungal agent.

One-year incidence, predictors, and accuracy of prediction of suicidal thoughts and behaviors from the first to second year of university.

BACKGROUND: Research is scarce on the prospective predictors of first onset suicidal thoughts and behaviors (STB) and the accuracy of these predictors in university students, particularly in low-and-middle income countries. Therefore, we assessed the 1-year incidence of STB among first-year students, a broad range of prospective predictors of STB incidence, and evaluated the prediction accuracy of a baseline multivariate risk prediction model to identify students at highest risk for STB onset over the subsequent 12 months. METHODS: Students (n = 3238) from 13 universities in Mexico completed an online survey developed for the World Mental Health International College Student Surveys in their first year and again 12 months after. We ran generalized linear models and receiver operator curves. RESULTS: The 1-year incidence of suicidal ideation, plan and attempt was 8.53%, 3.75%, and 1.16%, respectively. Predictors in final models were female sex (ideation only), minority sexual orientation (ideation only), depression, eating disorders, ADHD (ideation and plan), ongoing arguments or breakup with a romantic partner (ideation only), emotional abuse (ideation only), parental death (ideation, plan), not Catholic/Christian (ideation, plan), not having someone to rely on, psychotic experiences (plan only), and insufficient sleep (attempt only). Prediction accuracy for ideation, plan and attempt was area under the curve = 0.76, 0.81 and 0.78, respectively. Targeting the top 10% of students at highest risk could reduce STB in the subsequent year up to 36%. CONCLUSIONS: By assessing these risk/protective factors in incoming students we identified students at greatest risk for developing STB to whom suicide prevention strategies could be targeted.