RESUMEN

Status epilepticus (SE) is a medical emergency associated with high mortality and morbidity. Na+, K+-ATPase, is a promising therapeutic target for SE, given its critical role in regulation of neuron excitability and cellular homeostasis. We investigated the effects of a Na+, K+-ATPase-activating antibody (DRRSAb) on short-term electrophysiological and behavioral consequences of pilocarpine-induced SE. Rats were submitted to pilocarpine-induced SE, followed by intranasal administration (2 µg/nostril). The antibody increased EEG activity following SE, namely, EEG power in theta, beta, and gamma frequency bands, assessed by quantitative analysis of EEG power spectra. One week later, DRRSAb-treated animals displayed less behavioral hyperreactivity in pick-up tests and better performance in novel object recognition tests, indicating that the intranasal administration of this Na+, K+-ATPase activator immediately after SE improves behavioral outcomes at a later time point. These results suggest that Na+, K+-ATPase activation warrants further investigation as an adjunctive therapeutic strategy for SE.

Asunto(s)

Administración Intranasal , Electroencefalografía , Pilocarpina , ATPasa Intercambiadora de Sodio-Potasio , Estado Epiléptico , Animales , Estado Epiléptico/inducido químicamente , Estado Epiléptico/tratamiento farmacológico , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Masculino , Pilocarpina/farmacología , Electroencefalografía/métodos , Electroencefalografía/efectos de los fármacos , Ratas , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Ratas Wistar , Anticuerpos/farmacología , Anticuerpos/administración & dosificación

RESUMEN

Cryptococcus neoformans causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug against C. neoformans. BRI can affect the organization of the cell membrane, increasing the fungal cell permeability. We also investigated the effects of BRI against the model system Saccharomyces cerevisiae by analyzing libraries of mutants grown in the presence of BRI. In S. cerevisiae, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism. In vivo experiments show BRI significantly reduces C. neoformans survival inside macrophages and partially clears C. neoformans lung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against C. neoformans. BRI + CAS affects endocytic movement, calcineurin, and mitogen-activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis. IMPORTANCE: Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts, Cryptococcus neoformans and Cryptococcus gattii. There are few therapeutic options for treating cryptococcosis, and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a potential antifungal agent against C. neoformans. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. BRI alone was shown to inhibit the growth of C. neoformans, acting as a fungicidal drug, but surprisingly also potentiated the activity of caspofungin (CAS) against this species. We investigated the mechanism of action of BRI and BRI + CAS against C. neoformans. We propose BRI as a new antifungal agent against cryptococcosis.

Asunto(s)

Antifúngicos , Criptococosis , Cryptococcus neoformans , Saccharomyces cerevisiae , Antifúngicos/farmacología , Cryptococcus neoformans/efectos de los fármacos , Animales , Ratones , Criptococosis/tratamiento farmacológico , Criptococosis/microbiología , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genética , Modelos Animales de Enfermedad , Macrófagos/microbiología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Pruebas de Sensibilidad Microbiana , Caspofungina/farmacología , Femenino , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Anfotericina B/farmacología

RESUMEN

INTRODUCTION: This study assessed quit attempts among adults who use cigarettes either exclusively or with e-cigarettes in Mexico, where non-daily smoking predominates. METHODS: An open cohort of Mexican adults who smoke was surveyed every four months from November 2018 to March 2021. Participants followed to the next survey were analyzed (n = 2220 individuals, 4560 observations). Multinomial logistic models regressed smoking quit attempts reported at the followup survey (ref = no attempt; tried to quit; sustained attempt of ≥30 days) on e-cigarette use frequency (none = ref; 1-2 days/week; ≥3 days/week), adjusting for sociodemographics and smoking-related variables. Additional models subdivided e-cigarette users by intentions to quit smoking in the next six months (i.e., yes/no), use of nicotine (i.e., yes/no), and vaping device used (i.e., open/closed). RESULTS: At 4-month follow-up, 32.7 % had tried to quit, and 2.9 % had quit for 30 days or more. Compared to those who smoke exclusively, occasional, and frequent e-cigarette users were more likely to try to quit (Adjusted Relative Risk Ratio or ARRR = 1.26 and 1.66, respectively) but no more likely to sustain their quit attempt. Among those who intended to quit smoking, e-cigarette users were no more likely to either try or sustain quit attempts. Furthermore, use of e-cigarettes with nicotine (59.6 %) was unassociated with cessation except that those who frequently used e-cigarettes with nicotine were more likely to try to quit than those who smoke exclusively (ARRR = 1.88). Device type used was not differentially associated with outcomes. CONCLUSIONS: Mexicans who smoke and use e-cigarettes appear more likely than those who smoke exclusively to try to quit but not to sustain abstinence.

Asunto(s)

Sistemas Electrónicos de Liberación de Nicotina , Cese del Hábito de Fumar , Vapeo , Humanos , Cese del Hábito de Fumar/estadística & datos numéricos , Cese del Hábito de Fumar/psicología , Masculino , Femenino , México/epidemiología , Adulto , Vapeo/psicología , Vapeo/epidemiología , Estudios Longitudinales , Persona de Mediana Edad , Sistemas Electrónicos de Liberación de Nicotina/estadística & datos numéricos , Adulto Joven , Adolescente , Intención

RESUMEN

Predator non-consumptive effects (NCE) can alter prey foraging time and habitat use, potentially reducing fitness. Prey can mitigate NCEs by increasing vigilance, chewing-vigilance synchronization, and spatiotemporal avoidance of predators. We quantified the relationship between Mexican wolf (Canis lupus baileyi) predation risk and elk (Cervus canadensis) behavior. We conducted behavioral observations on adult female elk and developed predation risk indices using GPS collar data from Mexican wolves, locations of elk killed by wolves, and landscape covariates. We compared a priori models to determine the best predictors of adult female behavior and multitasking. Metrics that quantified both spatial and temporal predation risk were the most predictive. Vigilance was positively associated with increased predation risk. The effect of predation risk on foraging and resting differed across diurnal periods. During midday when wolf activity was lower, the probability of foraging increased while resting decreased in high-risk areas. During crepuscular periods when elk and wolves were most active, increased predation risk was associated with increased vigilance and slight decreases in foraging. Our results suggest elk are temporally avoiding predation risk from Mexican wolves by trading resting for foraging, a trade-off often not evaluated in behavioral studies. Probability of multitasking depended on canopy openness and an interaction between maternal period and predation risk; multitasking decreased prior to parturition and increased post parturition in high-risk areas. Openness was inversely related to multitasking. These results suggest adult female elk are altering the type of vigilance used depending on resource availability/quality, current energetic needs, and predation risk. Our results highlight potentially important, but often-excluded behaviors and trade-offs prey species may use to reduce the indirect effects of predation and contribute additional context to our understanding of predator-prey dynamics.

RESUMEN

INTRODUCTION: Heated tobacco products (HTPs) are promoted as less harmful than cigarettes; nonetheless, whether HTPs help smokers quit is uncertain. METHODS: Data from 4067 Mexican adult smokers surveyed longitudinally every four months (November 2019-March 2021) were analyzed. Mixed-effects multinomial models regressed HTP use frequency (no use=reference; monthly; weekly; and daily use) on sociodemographics and tobacco/nicotine-related variables. Among participants who completed at least two surveys (n=2900) over four months, the duration of their longest smoking quit attempt (SQA) between surveys (SQAs: <30 days; ≥30 days; no SQA=reference) was regressed on HTP use frequency, and changes in the number of cigarettes smoked per day were regressed on HTP initiation between surveys, adjusting for covariates. RESULTS: Consistent predictors of all HTP use frequencies (monthly, weekly, or daily vs no use) were daily smoking >5 cigarettes (ARRR=1.69 [95% CI: 1.12-2.55], 1.88 [95% CI: 1.26-2.81] and 6.46 [95% CI: 3.33-12.52], respectively); e-cigarette use (ARRR =5.68 [95% CI: 3.38-9.53], 6.54 [95% CI: 4.06-10.55] and 2.59 [95% CI: 1.26-5.30]); lower HTP risk perceptions (ARRR=2.12 [95% CI: 1.50-30.00], 2.25 [95% CI: 1.63-3.10] and 2.00 [95% CI: 1.25-3.22]); exposure to HTP information inside (ARRR=2.13 [95% CI: 1.44-3.15], 2.13 [95% CI: 1.49-3.05] and 3.72 [95% CI: 2.28-6.09]) and outside stores (ARRR=2.36 [95% CI: 1.56-3.57], 2.32 [95% CI: 1.65-3.25] and 2.44 [95% CI: 1.41-4.24]) where tobacco is sold; having family (ARRR=2.46 [95% CI: 1.54-3.91], 2.90 [95% CI: 1.93-4.37] and 2.96 [95% CI: 1.52-5.77]) and friends (ARRR=5.78 [95% CI: 3.60-9.30], 4.98 [95% CI: 3.22-7.72] and 6.61 [95% CI: 2.91-15.01]) who use HTPs. HTP use frequency was not associated with quit attempts, except for monthly HTP use predicting SQAs lasting ≥30 days (ARRR=2.12 [95% CI: 1.17-3.85]). Initiation of HTP use was not associated with changes in smoking frequency. Limiting analysis to those who intend to quit smoking also yielded null results. CONCLUSIONS: Among Mexican adult smokers, frequency of HTP use was mostly not associated with either cessation behaviors or changes in cigarette consumption, suggesting that HTPs have limited to no effectiveness for smoking cessation.

RESUMEN

Diisopentyl phthalate (DiPeP) is primarily used as a plasticizer or additive within the production of polyvinyl chloride (PVC), and has many additional industrial applications. Its metabolites were recently found in urinary samples of pregnant women; thus, this substance is of concern as relates to human exposure. Depending upon the nature of the alcohol used in its synthesis, DiPeP may exist either as a mixture consisting of several branched positional isomers, or as a single defined structure. This article investigates the skin sensitization potential and immunomodulatory effects of DiPeP CAS No. 84777-06-0, which is currently marketed and classified as a UVCB substance, by in silico and in vitro methods. Our findings showed an immunomodulatory effect for DiPeP in LPS-induced THP-1 activation assay (increased CD54 expression). In silico predictions using QSAR TOOLBOX 4.5, ToxTree, and VEGA did not identify DiPeP, in the form of a discrete compound, as a skin sensitizer. The keratinocyte activation (Key Event 2 (KE2) of the adverse outcome pathway (AOP) for skin sensitization) was evaluated by two different test methods (HaCaT assay and RHE assay), and results were discordant. While the HaCaT assay showed that DiPeP can activate keratinocytes (increased levels of IL-6, IL-8, IL-1α, and ILA gene expression), in the RHE assay, DiPeP slightly increased IL-6 release. Although inconclusive for KE2, the role of DiPeP in KE3 (dendritic cell activation) was demonstrated by the increased levels of CD54 and IL-8 and TNF-α in THP-1 cells (THP-1 activation assay). Altogether, findings were inconclusive regarding the skin sensitization potential of the UVCB DiPeP-disagreeing with the results of DiPeP in the form of discrete compound (skin sensitizer by the LLNA assay). Additional studies are needed to elucidate the differences between DiPeP isomer forms, and to better understand the applicability domains of non-animal methods in identifying skin sensitization hazards of UVCB substances.

Asunto(s)

Simulación por Computador , Queratinocitos , Ácidos Ftálicos , Humanos , Queratinocitos/efectos de los fármacos , Ácidos Ftálicos/toxicidad , Células HaCaT , Piel/efectos de los fármacos , Piel/inmunología , Piel/metabolismo , Relación Estructura-Actividad Cuantitativa , Plastificantes/toxicidad , Células THP-1 , Molécula 1 de Adhesión Intercelular/metabolismo , Molécula 1 de Adhesión Intercelular/genética , Línea Celular

RESUMEN

Plant microbiomes are known to serve several important functions for their host, and it is therefore important to understand their composition as well as the factors that may influence these microbial communities. The microbiome of Thalassia testudinum has only recently been explored, and studies to-date have primarily focused on characterizing the microbiome of plants in a single region. Here, we present the first characterization of the composition of the microbial communities of T. testudinum across a wide geographical range spanning three distinct regions with varying physicochemical conditions. We collected samples of leaves, roots, sediment, and water from six sites throughout the Atlantic Ocean, Caribbean Sea, and the Gulf of Mexico. We then analyzed these samples using 16S rRNA amplicon sequencing. We found that site and region can influence the microbial communities of T. testudinum, while maintaining a plant-associated core microbiome. A comprehensive comparison of available microbial community data from T. testudinum studies determined a core microbiome composed of 14 ASVs that consisted mostly of the family Rhodobacteraceae. The most abundant genera in the microbial communities included organisms with possible plant-beneficial functions, like plant-growth promoting taxa, disease suppressing taxa, and nitrogen fixers.

RESUMEN

Wildlife diseases have implications for ecology, conservation, human health, and health of domestic animals. They may impact wildlife health and population dynamics. Exposure rates of coyotes (Canis latrans) to pathogens such as Yersinia pestis, the cause of plague, may reflect prevalence rates in both rodent prey and human populations. We captured coyotes in north-central New Mexico during 2005-2008 and collected blood samples for serologic surveys. We tested for antibodies against canine distemper virus (CDV, Canine morbillivirus), canine parvovirus (CPV, Carnivore protoparvovirus), plague, tularemia (Francisella tularensis), and for canine heartworm (Dirofilaria immitis) antigen. Serum biochemistry variables that fell outside reference ranges were probably related to capture stress. We detected antibodies to parvovirus in 32/32 samples (100%), and to Y. pestis in 26/31 (84%). More than half 19/32 (59%) had antibodies against CDV, and 5/31 (39%) had antibodies against F. tularensis. We did not detect any heartworm antigens (n = 9). Pathogen prevalence was similar between sexes and among the three coyote packs in the study area. Parvovirus exposure appeared to happen early in life, and prevalence of antibodies against CDV increased with increasing age class. Exposure to Y. pestis and F. tularensis occurred across all age classes. The high coyote seroprevalence rates observed for CPV, Y. pestis, and CDV may indicate high prevalence in sympatric vertebrate populations, with implications for regional wildlife conservation as well as risk to humans via zoonotic transmission.

Asunto(s)

Coyotes , Virus del Moquillo Canino , Moquillo , Enfermedades de los Perros , Infecciones por Parvoviridae , Parvovirus Canino , Peste , Tularemia , Yersinia pestis , Animales , Perros , Humanos , Peste/epidemiología , Peste/veterinaria , Tularemia/epidemiología , Tularemia/veterinaria , Moquillo/epidemiología , Estudios Seroepidemiológicos , New Mexico , Anticuerpos Antivirales , Infecciones por Parvoviridae/epidemiología , Infecciones por Parvoviridae/veterinaria , Animales Salvajes

RESUMEN

OBJECTIVE: To determine whether nativity is associated with abdominal wall defects among births to Mexican-American women. STUDY DESIGN: Using a cross-sectional, population-based design, stratified and multivariable logistic regression analyses were performed on the 2014-2017 National Center for Health Statistics live-birth cohort dataset of infants of US-born (n = 1 398 719) and foreign-born (n = 1 221 411) Mexican-American women. RESULTS: The incidence of gastroschisis was greater among births to US-born compared with Mexico-born Mexican-American women: 36.7/100 000 vs 15.5/100 000, RR = 2.4 (2.0, 2.9). US-born (compared with Mexico-born) Mexican-American mothers had a greater percentage of teens and cigarette smokers, P < .0001. In both subgroups, gastroschisis rates were greatest among teens and decreased with advancing maternal age. Adjusting for maternal age, parity, education, cigarette smoking, pre-pregnancy body mass index, prenatal care usage, and infant sex), OR of gastroschisis for US-born (compared with Mexico-born) Mexican-American women was 1.7 (95% CI 1.4-2.0). The population attributable risk of maternal birth in the US for gastroschisis equaled 43%. The incidence of omphalocele did not vary by maternal nativity. CONCLUSIONS: Mexican-American women's birth in the US vs Mexico is an independent risk factor for gastroschisis but not omphalocele. Moreover, a substantial proportion of gastroschisis lesions among Mexican-American infants is attributable to factors closely related to their mother's nativity.

Asunto(s)

Gastrosquisis , Femenino , Humanos , Lactante , Embarazo , Estudios Transversales , Gastrosquisis/epidemiología , Gastrosquisis/etnología , Edad Materna , Americanos Mexicanos , Madres , Estados Unidos/epidemiología

RESUMEN

Cryptococcus gattii and Cryptococcus neoformans are the main etiological agents of cryptococcosis, an invasive mycosis treated with amphotericin B, 5-fluorocytosine, and fluconazole. This limited arsenal is toxic and is associated with antifungal resistance. Cryptococcosis and malaria pathogens are eukaryotic organisms that have a high incidence in Sub-Saharan Africa. The antimalarials (ATMs) halofantrine (HAL) and amodiaquine (AQ) block Plasmodium heme polymerase, and artesunate (ART) induces oxidative stress. Considering that Cryptococcus spp. is susceptible to reactive oxygen species and that iron is essential for metabolism, the repurposing of ATMs for treating cryptococcosis was tested. ATMs reduced fungal growth, induced oxidative and nitrosative stresses, and altered ergosterol content, melanin production, and polysaccharide capsule size in C. neoformans and C. gattii, revealing a dynamic effect on fungal physiology. A comprehensive chemical-genetic analysis using two mutant libraries demonstrated that the deletion of genes involved in synthesizing components of the plasma membrane and cell wall, and oxidative stress responses are essential for fungal susceptibility to ATMs. Interestingly, the amphotericin B (AMB) fungicidal concentrations were ∼10 times lower when combined with ATMs, demonstrating a synergistic interaction. Further, the combinations showed reduced toxicity to murine macrophages. Finally, HAL+AMB and AQ+AMB efficiently reduced lethality and fungal burden in the lungs and brain in murine cryptococcosis. These findings provide perspectives for further studies with ATMs against cryptococcosis and other fungal infections.

Asunto(s)

Antimaláricos , Criptococosis , Cryptococcus gattii , Cryptococcus neoformans , Animales , Ratones , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Antifúngicos/metabolismo , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Antimaláricos/metabolismo , Criptococosis/tratamiento farmacológico , Criptococosis/microbiología , Fluconazol/farmacología , Fluconazol/uso terapéutico , Pruebas de Sensibilidad Microbiana

RESUMEN

PURPOSE: To determine the relationships between impact of secondary health conditions (SHCs), treatment of SHCs, and life satisfaction (LS) following spinal cord injury (SCI) across 21 countries. Hypotheses were as follows: (1) Persons with SCI and fewer SHCs report higher LS and (2) Persons who receive treatment for SHCs report higher LS than those who do not receive treatment. METHODS: Cross-sectional survey, including 10,499 persons with traumatic or non-traumatic SCI aged 18 years or older and living in the community. To assess SHCs, 14 items adapted from the SCI-Secondary Conditions Scale were used (range 1-5). SHCs index was calculated as the mean of all 14 items. LS was assessed using a selection of 5 items from the World Health Organization Quality of Life Assessment. LS index was calculated as the mean of these 5 items. RESULTS: South Korea, Germany, and Poland exhibited the highest (2.40-2.93) and Brazil, China, and Thailand the lowest (1.79-1.90) impact of SHCs. Indexes for LS and SHCs were inversely correlated (- 0.418; p < 0.001). Mixed Model Analysis showed that the fixed effect (key predictors of the study) of SHCs index (p < 0.001) and the positive interaction between SHCs index and treatment (p = 0.002) were significant determinants of LS. CONCLUSION: Persons with SCI across the world are more likely to perceive better LS if they experience fewer SHCs and receive treatment for SHCs, in comparison to those who do not. Prevention and treatment of SHCs following SCI should be a high priority in order to improve the lived experience and enhance LS.

Asunto(s)

Calidad de Vida , Traumatismos de la Médula Espinal , Humanos , Calidad de Vida/psicología , Estudios Transversales , Traumatismos de la Médula Espinal/rehabilitación , Satisfacción Personal , Brasil

RESUMEN

OBJECTIVE: To determine the whether a greater percentage of deaths of infants born at term among US-born (vs foreign-born) women is attributable to paternal nonacknowledgement. STUDY DESIGN: Using a cross-sectional population-based design, stratified and multivariable binomial regression analyses were performed on a subset of the 2017 National Center for Health Statistics linked live birth-infant death cohort dataset of singleton infants born at term (37-42 weeks) of US-born (N = 2 127 243) and foreign-born (N = 334 664) women. RESULTS: Infants of US-born women had a prevalence of paternal nonacknowledgement of 11.3% vs 7.5% for foreign-born women, P < .001. The infant mortality rate of term births to US-born women with paternal nonacknowledgment equaled 5.0/1000 vs 2.0/1000 for those with paternal acknowledgment; relative risk (RR) = 2.47 (2.31, 2.86). The infant mortality rate of term births to foreign-born women with paternal nonacknowledgment equaled 2.5/1000 vs 1.6/1000 for those with paternal acknowledgment, RR = 1.61 (1.24, 2.10). The adjusted (controlling for selected covariates) RR of first-year mortality of term births among US-born and foreign-born women with nonacknowledged (vs acknowledged) fathers equaled 1.43 (1.33, 1.54) and 1.38 (1.04, 1.84), respectively. The population-attributable risk percent of deaths in infants born at term for paternal nonacknowledgement among US-born and foreign-born women equaled 4.9% (246 deaths) and 2.8% (15 deaths), respectively. CONCLUSIONS: Paternal nonacknowledgement is associated with a 40% greater infant mortality rate among term births to US-born and foreign-born women; however, a greater proportion of first-year deaths among term births to US-born (vs foreign-born) women is attributable to paternal nonacknowledgment. These findings highlight the importance of a father's involvement in the outcomes of infants born at term.

Asunto(s)

Padre , Mortalidad Infantil , Masculino , Lactante , Humanos , Femenino , Estudios Transversales , Análisis de Regresión

RESUMEN

Pest control methods that can target pest species with limited environmental impacts are a conservation and economic priority. Species-specific pest control using RNA interference is a challenging but promising avenue in developing the next generation of pest management. We investigate the feasibility of manipulating a biological invader's immune system using double-stranded RNA (dsRNA) in order to increase susceptibility to naturally occurring pathogens. We used the invasive Argentine ant as a model, targeting the immunity-associated genes Spaetzle and Dicer-1 with dsRNA. We show that feeding with Spaetzle dsRNA can result in partial target gene silencing for up to 28 days in the laboratory and 5 days in the field. Dicer-1 dsRNA only resulted in partial gene knockdown after 2 days in the laboratory. Double-stranded RNA treatments were associated with significant gene expression disruptions across immune pathways in the laboratory and to a lower extent in the field. In total, 12 viruses and four bacteria were found in these ant populations. Some changes in viral loads in dsRNA-treated groups were observed. For example, Linepithema humile Polycipivirus 2 (LhuPCV2) loads increased after 2 days of treatment with Spaetzle and Dicer-1 dsRNA treatments in the laboratory. After treatment with the dsRNA in the field, after 5 days the virus Linepithema humile toti-like virus 1 (LhuTLV1) was significantly more abundant. However, immune pathway disruption did not result in a consistent increase in microbial infections, nor did it alter ant abundance in the field. Some viruses even declined in abundance after dsRNA treatment. Our study explored the feasibility of lowering a pest's immunity as a control tool. We demonstrate that it is possible to alter immune gene expression of pest species and pathogen loads, although in our specific system the affected pathogens did not appear to influence pest abundance. We provide suggestions on future directions for dsRNA-mediated immune disruption in pest species, including potential avenues to improve dsRNA delivery as well as the importance of pest and pathogen biology. Double-stranded RNA targeting immune function might be especially useful for pest control in systems in which viruses or other microorganisms are prevalent and have the potential to be pathogenic.

Asunto(s)

Hormigas , Virus , Animales , ARN Bicatenario , Silenciador del Gen , Interferencia de ARN , Virus/genética

RESUMEN

The phenotypic plasticity of Cryptococcus neoformans is widely studied and demonstrated in vitro, but its influence on pathogenicity remains unclear. In this study, we investigated the dynamics of cryptococcal cell and transcriptional remodeling during pulmonary infection in a murine model. We showed that in Cryptococcus neoformans, cell size reduction (cell body ≤ 3 µm) is important for initial adaptation during infection. This change was associated with reproductive fitness and tissue invasion. Subsequently, the fungus develops mechanisms aimed at resistance to the host's immune response, which is determinant for virulence. We investigated the transcriptional changes involved in this cellular remodeling and found an upregulation of transcripts related to ribosome biogenesis at the beginning (6 h) of infection and a later (10 days) upregulation of transcripts involved in the inositol pathway, energy production, and the proteasome. Consistent with a role for the proteasome, we found that its inhibition delayed cell remodeling during infection with the H99 strain. Altogether, these results further our understanding of the infection biology of C. neoformans and provide perspectives to support therapeutic and diagnostic targets for cryptococcosis.

Asunto(s)

Criptococosis , Cryptococcus neoformans , Ratones , Animales , Cryptococcus neoformans/genética , Cryptococcus neoformans/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Modelos Animales de Enfermedad , Criptococosis/microbiología , Virulencia

RESUMEN

The field of plastic surgery, formally organized in 1931 with the founding of the American Society of Plastic and Reconstructive Surgery, was shaped in many ways by a small practice of Philadelphia physicians. At the center of the practice was Warren B. Davis, a Philadelphia otolaryngologist and plastics pioneer whose innovations in cleft palate surgery would lead to significant improvements in functional and cosmetic outcomes in his time. In addition to his own innovations, Davis was responsible for the training of John Reese, the inventor of the Reese dermatome that changed the face of burn medicine during World War II. Aside from his contributions to surgery and the founding of the American Society of Plastic and Reconstructive Surgery, Dr. Davis was also the founder and first editor of the Plastic and Reconstructive Surgery journal which to this day is the premiere, authoritative journal of plastic surgery. Lastly, Dr. Davis established a plastic surgical practice, now Jefferson Plastic Surgery. Unique in its longevity, this practice would continue to shape the field of plastic surgery and continues to improve lives today-109 years after its founding in 1913.

RESUMEN

As currently circumscribed, Acrogenospora (Acrogenosporaceae, Minutisphaerales, Dothideomycetes) is a genus of saprobic hyphomycetes with distinctive conidia. Although considered common and cosmopolitan, the genus is poorly represented by sequence data, and no neotropical representatives are present in public sequence databases. Consequently, Acrogenospora has been largely invisible to ecological studies that rely on sequence-based identification. As part of an effort to identify fungi collected during ecological studies, we identified strains of Acrogenospora isolated in culture from seeds in the soil seed bank of a lowland tropical forest in Panama. Here we describe Acrogenospora terricola sp. nov. based on morphological and phylogenetic analyses. We confirm that the genus has a pantropical distribution. The observation of Acrogenospora infecting seeds in a terrestrial environment contrasts with previously described species in the genus, most of which occur on decaying wood in freshwater environments. This work highlights the often hidden taxonomic value of collections derived from ecological studies of fungal communities and the ways in which rich sequence databases can shed light on the identity, distributions and diversity of cryptic microfungi.

Asunto(s)

Ascomicetos , Banco de Semillas , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Bosques , Filogenia , ARN Ribosómico 16S/genética , Semillas/microbiología , Análisis de Secuencia de ADN , Suelo , Clima Tropical , Panamá

RESUMEN

The phylogeography of the American black bear (Ursus americanus) is characterized by isolation into glacial refugia, followed by population expansion and genetic admixture. Anthropogenic activities, including overharvest, habitat loss, and transportation infrastructure, have also influenced their landscape genetic structure. We describe the genetic structure of the American black bear in the American Southwest and northern Mexico and investigate how prehistoric and contemporary forces shaped genetic structure and influenced gene flow. Using a suite of microsatellites and a sample of 550 bears, we identified 14 subpopulations organized hierarchically following the distribution of ecoregions and mountain ranges containing black bear habitat. The pattern of subdivision we observed is more likely a product of postglacial habitat fragmentation during the Pleistocene and Holocene, rather than a consequence of contemporary anthropogenic barriers to movement during the Anthropocene. We used linear mixed-effects models to quantify the relationship between landscape resistance and genetic distance among individuals, which indicated that both isolation by resistance and geographic distance govern gene flow. Gene flow was highest among subpopulations occupying large tracts of contiguous habitat, was reduced among subpopulations in the Madrean Sky Island Archipelago, where montane habitat exists within a lowland matrix of arid lands, and was essentially nonexistent between two isolated subpopulations. We found significant asymmetric gene flow supporting the hypothesis that bears expanded northward from a Pleistocene refugium located in the American Southwest and northern Mexico and that major highways were not yet affecting gene flow. The potential vulnerability of the species to climate change, transportation infrastructure, and the US-Mexico border wall highlights conservation challenges and opportunities for binational collaboration.

RESUMEN

Although Central America is largely dengue virus (DENV)-endemic, the 2015-2016 Zika virus (ZIKV) pandemic brought new urgency to develop surveillance approaches capable of characterizing the rapidly changing disease burden in resource-limited settings. We conducted a pediatric DENV surveillance study in rural Guatemala, including serial cross-sectional surveys from April through September 2015 (Survey 1), in October-November 2015 (Survey 2), and January-February 2016 (Survey 3). Serum underwent DENV IgM MAC ELISA and polymerase chain reaction testing. Using banked specimens from Surveys 2 and 3, we expanded testing to include DENV 1-4 and ZIKV microneutralization (MN50), DENV NS1 IgG ELISA, and ZIKV anti-NS1 antibody Blockage of Binding (BoB) ELISA testing. Demographic risk factors for ZIKV BoB positivity were explored using multivariable generalized linear regression models. Of Survey 2 and 3 samples available (N = 382), DENV seroprevalence slightly increased (+1%-10% depending on the assay) during the surveillance period and increased with age. In contrast, ZIKV seroprevalence consistently increased over the 3-month period, including from 6% to 34% (P < 0.0001) and 10%-37% (P < 0.0001) using the MN50 ≥100 and BoB ELISA assays, respectively. Independent risk factors for ZIKV seropositivity included older age (prevalence ratio (PR)/year = 1.12, 95% confidence interval (CI) = 1.07-1.17) and primary caregiver literacy (PR = 2.80, CI = 1.30-6.06). Rapid active surveillance (RAS) surveys demonstrated a nearly 30% increase in ZIKV prevalence and a slight (≤ 10%) increase in DENV seroprevalence from October to November 2015 to January to February 2016 in rural southwest Guatemala, regardless of serologic assay used. RAS surveys may be a useful "off-the-shelf" tool to characterize arboviruses and other emerging pathogens rapidly in resource-limited settings.

Asunto(s)

Virus del Dengue , Dengue , Infección por el Virus Zika , Virus Zika , Niño , Humanos , Estudios Seroepidemiológicos , Estudios Transversales , Guatemala/epidemiología , Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática , Reacciones Cruzadas

RESUMEN

Background: Across the globe, there are successful health innovations that could help improve public health in US communities at lower cost and with higher effectiveness than standard practice. However, which factors should be considered to heighten the likelihood of successful transfer of global health ideas to the US still warrants more empirical investigation. Objective: This study aimed to develop a conceptual framework delineating important factors to be considered for successful introduction of global health innovations to US communities, based on diffusion of innovations literature and case studies of global health innovations that have been adopted in US communities. Methods: Five global health innovations adopted in US communities were selected based on expert panel recommendations and a review of academic and gray literatures. These innovations had diverse origins (Columbia, Mexico, South Africa, Sweden, and Wales) and exhibited various means of achieving desired health outcomes. We conducted archival research and 27 interviews (42 interviewees) with leaders and stakeholders of the five innovations to identify important factors for the transfer of global health innovations to the US. Findings: Six factors were determined to be important for global health innovation adoption in the US: (1) innovation attributes, (2) linking agents, (3) inter-organizational partnerships, (4) scale up strategies, (5) implementation processes and outcomes in US communities, and (6) policy and social context. These factors correspond well to factors emphasized in the diffusion of innovation literature, although the importance of some sub-factors (e.g., stigma regarding the origin of innovations) diverged from the literature. Conclusions: Based on our findings, we developed the Designing for Diffusion Framework for Global Health Innovations. The framework provides a comprehensive picture of factors that can be facilitators or hindrances for moving a global health innovation to the US to help smooth the diffusion process for better adoption and implementation in US communities.

Asunto(s)

Difusión de Innovaciones , Salud Global , Humanos , México , Sudáfrica

RESUMEN

OBJECTIVE: To determine whether differential exposure to an adverse maternal fetal environment partially explains disparate outcomes in infants with major congenital heart disease (CHD). STUDY DESIGN: Retrospective cohort study utilizing a population-based administrative California database (2011-2017). Primary exposure: Race/ethnicity. Primary mediator: Adverse maternal fetal environment (evidence of maternal metabolic syndrome and/or maternal placental syndrome). OUTCOMES: Composite of 1-year mortality or severe morbidity and days alive out of hospital in the first year of life (DAOOH). Mediation analyses determined the percent contributions of mediators on pathways between race/ethnicity and outcomes after adjusting for CHD severity. RESULTS: Included were 2747 non-Hispanic White infants (reference group), 5244 Hispanic, and 625 non-Hispanic Black infants. Hispanic and non-Hispanic Black infants had a higher risk for composite outcome (crude OR: 1.18; crude OR: 1.25, respectively) and fewer DAOOH (-6 & -12 days, respectively). Compared with the reference group, Hispanic infants had higher maternal metabolic syndrome exposure (43% vs 28%, OR: 1.89), and non-Hispanic Black infants had higher maternal metabolic syndrome (44% vs 28%; OR: 1.97) and maternal placental syndrome exposure (18% vs 12%; OR, 1.66). Both maternal metabolic syndrome exposure (OR: 1.21) and maternal placental syndrome exposure (OR: 1.56) were related to composite outcome and fewer DAOOH (-25 & -16 days, respectively). Adverse maternal fetal environment explained 25% of the disparate relationship between non-Hispanic Black race and composite outcome and 18% of the disparate relationship between Hispanic ethnicity and composite outcome. Adverse maternal fetal environment explained 16% (non-Hispanic Black race) and 21% (Hispanic ethnicity) of the association with DAOOH. CONCLUSIONS: Increased exposure to adverse maternal fetal environment contributes to racial and ethnic disparities in major CHD outcomes.

Asunto(s)

Cardiopatías Congénitas , Síndrome Metabólico , Lactante , Recién Nacido , Femenino , Embarazo , Humanos , Estudios Retrospectivos , Placenta , Hispánicos o Latinos