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1.
Radiat Res ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39021204

RESUMEN

In this article we review the history of key epidemiological studies of populations exposed to ionizing radiation. We highlight historical and recent findings regarding radiation-associated risks for incidence and mortality of cancer and non-cancer outcomes with emphasis on study design and methods of exposure assessment and dose estimation along with brief consideration of sources of bias for a few of the more important studies. We examine the findings from the epidemiological studies of the Japanese atomic bomb survivors, persons exposed to radiation for diagnostic or therapeutic purposes, those exposed to environmental sources including Chornobyl and other reactor accidents, and occupationally exposed cohorts. We also summarize results of pooled studies. These summaries are necessarily brief, but we provide references to more detailed information. We discuss possible future directions of study, to include assessment of susceptible populations, and possible new populations, data sources, study designs and methods of analysis.

2.
Nat Commun ; 15(1): 6107, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39030220

RESUMEN

Electrostatic capacitors play a crucial role as energy storage devices in modern electrical systems. Energy density, the figure of merit for electrostatic capacitors, is primarily determined by the choice of dielectric material. Most industry-grade polymer dielectrics are flexible polyolefins or rigid aromatics, possessing high energy density or high thermal stability, but not both. Here, we employ artificial intelligence (AI), established polymer chemistry, and molecular engineering to discover a suite of dielectrics in the polynorbornene and polyimide families. Many of the discovered dielectrics exhibit high thermal stability and high energy density over a broad temperature range. One such dielectric displays an energy density of 8.3 J cc-1 at 200 °C, a value 11 × that of any commercially available polymer dielectric at this temperature. We also evaluate pathways to further enhance the polynorbornene and polyimide families, enabling these capacitors to perform well in demanding applications (e.g., aerospace) while being environmentally sustainable. These findings expand the potential applications of electrostatic capacitors within the 85-200 °C temperature range, at which there is presently no good commercial solution. More broadly, this research demonstrates the impact of AI on chemical structure generation and property prediction, highlighting the potential for materials design advancement beyond electrostatic capacitors.

3.
iScience ; 27(6): 110038, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38883830

RESUMEN

Supplementing influenza vaccines with additional protective antigens such as neuraminidase (NA) is a promising strategy for increasing the breadth of the immune response. Here, we improved the immunogenicity and stability of secreted recombinant NA (rNA) tetramers by covalently conjugating them onto the surface of AP205 capsid virus-like particles (cVLPs) using a Tag/Catcher ligation system. cVLP display increased the induction of IgG2a subclass anti-NA antibodies, which exhibited cross-reactivity with an antigenically distant homologous NA. It also reduced the single dose rNA amounts needed for protection against viral challenge in mice, demonstrating a dose-sparing effect. Moreover, effective cVLP-display was achieved across different NA subtypes, even when the conjugation was performed shortly before administration. Notably, the rNA-cVLP immunogenicity was retained upon mixing or co-administering with commercial vaccines. These results highlight the potential of this approach for bolstering the protective immune responses elicited by influenza vaccines.

4.
Angew Chem Int Ed Engl ; 63(29): e202403133, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38713874

RESUMEN

Sialosides containing C8-modified sialic acids are challenging synthetic targets but potentially useful probes for diagnostic substrate profiling of sialidases and elucidating the binding specificity of sialic acid-interacting proteins. Here, we demonstrate efficient chemoenzymatic methods for synthesizing para-nitrophenol-tagged α2-3- and α2-6-linked sialyl galactosides containing C8-acetamido, C8-azido, or C8-amino derivatized N-acetylneuraminic acid (Neu5Ac). High-throughput substrate specificity studies showed that the C8-modification of sialic acid significantly changes its recognition by sialidases from humans, various bacteria, and different influenza A and B viruses. Sialosides carrying Neu5Ac with a C8-azido modification were generally well tolerated by all the sialidases we tested, whereas sialosides containing C8-acetamido-modified Neu5Ac were only cleaved by selective bacterial sialidases. In contrast, sialosides with C8-amino-modified Neu5Ac were cleaved by a combination of selective bacterial and influenza A virus sialidases. These results indicate that sialosides terminated with a C8-amino or C8-acetamido-modified sialic acid can be used with other sialosides for diagnostic profiling of disease-causing sialidase-producing pathogens.


Asunto(s)
Neuraminidasa , Ácidos Siálicos , Neuraminidasa/metabolismo , Especificidad por Sustrato , Humanos , Ácidos Siálicos/química , Ácidos Siálicos/metabolismo , Ácido N-Acetilneuramínico/química , Ácido N-Acetilneuramínico/metabolismo , Bacterias/enzimología , Orthomyxoviridae/enzimología , Virus de la Influenza A/enzimología
5.
Artículo en Inglés | MEDLINE | ID: mdl-38141291

RESUMEN

Recombinant protein-based approaches are ideally suited for producing vaccine antigens that are not overly abundant in viruses, such as influenza neuraminidase (NA). However, obtaining sufficient quantities of recombinant viral surface antigens remains challenging, often resulting in the use of chimeric proteins with affinity tags that can invariably impact the antigen's properties. Here, we developed multistep chromatography approaches for purifying secreted recombinant NA (rNA) antigens that are derived from recent H1N1 and H3N2 viruses and produced using insect cells. Analytical analyses showed that these isolation procedures yielded homogenous tetrameric rNA preparations with consistent specific activities that were not possible from a common immobilized metal affinity chromatography purification procedure. The use of classical chromatography improved the rNA tetramer homogeneity by removing the requirement of the N-terminal poly-histidine affinity tag that was shown to promote higher order rNA oligomer formation. In addition, these procedures reduced the specific activity variation by eliminating the exposure to Ni2+ ions and imidazole, with the latter showing pH and NA subtype dependent effects. Together, these results demonstrate that purification by multistep chromatography improves the homogeneity of secreted rNAs and eliminates the need for affinity tag-based approaches that can potentially alter the properties of these recombinant antigens.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Humanos , Neuraminidasa/genética , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/metabolismo , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/metabolismo , Proteínas Recombinantes/genética , Cromatografía , ARN
7.
BMJ ; 382: e074520, 2023 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-37586731

RESUMEN

OBJECTIVE: To evaluate the effect of protracted low dose, low dose rate exposure to ionising radiation on the risk of cancer. DESIGN: Multinational cohort study. SETTING: Cohorts of workers in the nuclear industry in France, the UK, and the US included in a major update to the International Nuclear Workers Study (INWORKS). PARTICIPANTS: 309 932 workers with individual monitoring data for external exposure to ionising radiation and a total follow-up of 10.7 million person years. MAIN OUTCOME MEASURES: Estimates of excess relative rate per gray (Gy) of radiation dose for mortality from cancer. RESULTS: The study included 103 553 deaths, of which 28 089 were due to solid cancers. The estimated rate of mortality due to solid cancer increased with cumulative dose by 52% (90% confidence interval 27% to 77%) per Gy, lagged by 10 years. Restricting the analysis to the low cumulative dose range (0-100 mGy) approximately doubled the estimate of association (and increased the width of its confidence interval), as did restricting the analysis to workers hired in the more recent years of operations when estimates of occupational external penetrating radiation dose were recorded more accurately. Exclusion of deaths from lung cancer and pleural cancer had a modest effect on the estimated magnitude of association, providing indirect evidence that the association was not substantially confounded by smoking or occupational exposure to asbestos. CONCLUSIONS: This major update to INWORKS provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality based on some of the world's most informative cohorts of radiation workers. The summary estimate of excess relative rate solid cancer mortality per Gy is larger than estimates currently informing radiation protection, and some evidence suggests a steeper slope for the dose-response association in the low dose range than over the full dose range. These results can help to strengthen radiation protection, especially for low dose exposures that are of primary interest in contemporary medical, occupational, and environmental settings.


Asunto(s)
Neoplasias Inducidas por Radiación , Enfermedades Profesionales , Exposición Profesional , Exposición a la Radiación , Humanos , Estados Unidos , Estudios de Cohortes , Dosis de Radiación , Radiación Ionizante , Industrias , Reino Unido/epidemiología , Exposición Profesional/efectos adversos , Exposición a la Radiación/efectos adversos
8.
Saf Health Work ; 14(2): 141-152, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37389311

RESUMEN

Objective: We performed a meta-analysis of epidemiological results for the association between occupational exposure as a firefighter and cancer as part of the broader evidence synthesis work of the IARCMonographs program. Methods: A systematic literature search was conducted to identify cohort studies of firefighters followed for cancer incidence and mortality. Studies were evaluated for the influence of key biases on results. Random-effects meta-analysis models were used to estimate the association between ever-employment and duration of employment as a firefighter and risk of 12 selected cancers. The impact of bias was explored in sensitivity analyses. Results: Among the 16 included cancer incidence studies, the estimated meta-rate ratio, 95% confidence interval (CI), and heterogeneity statistic (I2) for ever-employment as a career firefighter compared mostly to general populations were 1.58 (1.14-2.20, 8%) for mesothelioma, 1.16 (1.08-1.26, 0%) for bladder cancer, 1.21 (1.12-1.32, 81%) for prostate cancer, 1.37 (1.03-1.82, 56%) for testicular cancer, 1.19 (1.07-1.32, 37%) for colon cancer, 1.36 (1.15-1.62, 83%) for melanoma, 1.12 (1.01-1.25, 0%) for non-Hodgkin lymphoma, 1.28 (1.02-1.61, 40%) for thyroid cancer, and 1.09 (0.92-1.29, 55%) for kidney cancer. Ever-employment as a firefighter was not positively associated with lung, nervous system, or stomach cancer. Results for mesothelioma and bladder cancer exhibited low heterogeneity and were largely robust across sensitivity analyses. Conclusions: There is epidemiological evidence to support a causal relationship between occupational exposure as a firefighter and certain cancers. Challenges persist in the body of evidence related to the quality of exposure assessment, confounding, and medical surveillance bias.

9.
Vaccine ; 41(29): 4302-4312, 2023 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-37301705

RESUMEN

Most seasonal influenza vaccines are produced using hemagglutinin (HA) surface antigens from inactivated virions. However, virions are thought to be a suboptimal source for the less abundant neuraminidase (NA) surface antigen, which is also protective against severe disease. Here, we demonstrate that inactivated influenza virions are compatible with two modern approaches for improving protective antibody responses against NA. Using a DBA/2J mouse model, we show that the strong infection-induced NA inhibitory (NAI) antibody responses are only achieved by high dose immunizations of inactivated virions, likely due to the low viral NA content. Based on this observation, we first produced virions with higher NA content by using reverse genetics to exchange the viral internal gene segments. Single immunizations with these inactivated virions showed enhanced NAI antibody responses and improved NA-based protection from a lethal viral challenge while also allowing for the development of natural immunity to the heterotypic challenge virus HA. Second, we combined inactivated virions with recombinant NA protein antigens. These combination vaccines increased NA-based protection following viral challenge and elicited stronger antibody responses against NA than either component alone, especially when the NAs possessed similar antigenicity. Together, these results indicate that inactivated virions are a flexible platform that can be easily combined with protein-based vaccines to improve protective antibody responses against influenza antigens.


Asunto(s)
Vacunas contra la Influenza , Gripe Humana , Infecciones por Orthomyxoviridae , Animales , Ratones , Humanos , Neuraminidasa , Formación de Anticuerpos , Anticuerpos Antivirales , Ratones Endogámicos DBA , Proteínas Recombinantes , Glicoproteínas Hemaglutininas del Virus de la Influenza
10.
Int J Epidemiol ; 52(4): 1015-1024, 2023 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-37253388

RESUMEN

BACKGROUND: The risk of solid cancers from low-level protracted ionizing radiation is not well characterized. Nuclear workers provide valuable information on the effects of ionizing radiation in contemporary exposure scenarios relevant to workers and the public. METHODS: We evaluated the association between penetrating ionizing radiation exposure and solid cancer mortality among a pooled cohort of nuclear workers in the USA, with extended follow-up to examine cancers with long latencies. This analysis includes 101 363 workers from five nuclear facilities, with 12 069 solid cancer deaths between 1944 and 2016. The association between cumulative equivalent dose measured in sieverts (Sv) and solid cancer subtypes were modelled as the excess relative rate per Sv (ERR Sv-1) using Cox regression. RESULTS: For the association between ionizing radiation exposure and all solid cancer mortality we observed an elevated rate (ERR Sv-1=0.19; 95% CI: -0.10, 0.52), which was higher among a contemporary sub-cohort of workers first hired in 1960 or later (ERR Sv-1= 2.23; 95% CI: 1.13, 3.49). Similarly, we observed an elevated rate for lung cancer mortality (ERR Sv-1= 0.65; 95% CI: 0.09, 1.30) that was higher among contemporary hires (ERR Sv-1= 2.90; 95% CI: 1.00, 5.26). CONCLUSIONS: Although concerns remain about confounding, measurement error and precision, this analysis strengthens the evidence base indicating there are radiogenic risks for several solid cancer types.


Asunto(s)
Neoplasias Inducidas por Radiación , Enfermedades Profesionales , Exposición Profesional , Exposición a la Radiación , Humanos , Radiación Ionizante , Exposición Profesional/efectos adversos
11.
Artículo en Inglés | MEDLINE | ID: mdl-37113193

RESUMEN

Objective: Antimicrobial stewardship has special challenges in particular populations and facilities, including pediatrics. We sought to augment the information available to antimicrobial stewardship programs (ASPs) by created a cumulative statewide antibiogram for neonatal and pediatric populations. Methods: In the Antimicrobial Stewardship Collaborative of South Carolina (ASC-SC), we created statewide antibiograms, including a separate antibiogram accounting for the pediatric and neonatal intensive care unit (NICU) populations. We collated data from the 4 pediatric and 3 NICU facilities in the state to provide a cumulative statewide antibiogram. Results: Methicillin-susceptible Staphylococcus aureus was more prevalent than methicillin-resistant Staphylococcus aureus. Pseudomonas aeruginosa, Citrobacter koserii, and Acinetobacter baumannii were isolated in only 1 NICU. Conclusions: These antibiograms should improve empiric prescribing in both the inpatient and outpatient setting, providing data in some areas that historically do not have pediatric antibiogram to inform prescribing. The antibiogram alone is not sufficient independently to improve prescribing but is one important aspect of stewardship in the pediatric population of South Carolina.

12.
Nano Lett ; 23(8): 3377-3384, 2023 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-37040311

RESUMEN

Many cellular processes involve the lateral organization of integral and peripheral membrane proteins into nanoscale domains. Despite the biological significance, the mechanisms that facilitate membrane protein clustering into nanoscale lipid domains remain enigmatic. In cells, the analysis of membrane protein phase affinity is complicated by the size and temporal nature of ordered and disordered lipid domains. To overcome these limitations, we developed a method for delivering membrane proteins from transfected cells into phase-separated model membranes that combines optical trapping with thermoplasmonic-mediated membrane fusion and confocal imaging. Using this approach, we observed clear phase partitioning into the liquid disordered phase following the transfer of GFP-tagged influenza hemagglutinin and neuraminidase from transfected cell membranes to giant unilamellar vesicles. The generic platform presented here allows investigation of the phase affinity of any plasma membrane protein which can be labeled or tagged with a fluorescent marker.


Asunto(s)
Gripe Humana , Glicoproteína de la Espiga del Coronavirus , Humanos , Fusión de Membrana , Membrana Celular/metabolismo , Proteínas de la Membrana/metabolismo , Lípidos
13.
Occup Environ Med ; 80(6): 297-303, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36972975

RESUMEN

OBJECTIVE: To compare mortality rates in World Trade Center (WTC)-exposed Fire Department of the City of New York (FDNY) firefighters with rates in similarly healthy, non-WTC-exposed/non-FDNY firefighters, and compare mortality in each firefighter cohort with the general population. METHODS: 10 786 male WTC-exposed FDNY firefighters and 8813 male non-WTC-exposed firefighters from other urban fire departments who were employed on 11 September 2001 were included in the analyses. Only WTC-exposed firefighters received health monitoring via the WTC Health Programme (WTCHP). Follow-up began 11 September 2001 and ended at the earlier of death date or 31 December 2016. Death data were obtained from the National Death Index and demographics from the fire departments. We estimated standardised mortality ratios (SMRs) in each firefighter cohort versus US males using demographic-specific US mortality rates. Poisson regression models estimated relative rates (RRs) of all-cause and cause-specific mortality in WTC-exposed versus non-WTC-exposed firefighters, controlling for age and race. RESULTS: Between 11 September 2001 and 31 December 2016, there were 261 deaths among WTC-exposed firefighters and 605 among non-WTC-exposed. Both cohorts had reduced all-cause mortality compared with US males (SMR (95% CI)=0.30 (0.26 to 0.34) and 0.60 (0.55 to 0.65) in WTC-exposed and non-WTC-exposed, respectively). WTC-exposed firefighters also had lower rates of all-cause mortality (RR=0.54, 95% CI=0.49 to 0.59) and cancer-specific, cardiovascular-specific and respiratory disease-specific mortality compared with non-WTC-exposed firefighters. CONCLUSION: Both firefighter cohorts had lower than expected all-cause mortality. Fifteen years post 11 September 2001, mortality was lower in WTC-exposed versus non-WTC-exposed firefighters. Lower mortality in the WTC-exposed suggests not just a healthy worker effect, but additional factors such as greater access to free health monitoring and treatment that they receive via the WTCHP.


Asunto(s)
Bomberos , Neoplasias , Exposición Profesional , Ataques Terroristas del 11 de Septiembre , Humanos , Masculino , Trabajo de Rescate , Causas de Muerte , New York/epidemiología , Neoplasias/epidemiología , Exposición Profesional/efectos adversos , Ciudad de Nueva York/epidemiología
14.
J Biol Chem ; 299(2): 102891, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36634846

RESUMEN

Influenza A viruses and the bacterium Streptococcus pneumoniae (pneumococci) both express neuraminidases that catalyze release of sialic acid residues from oligosaccharides and glycoproteins. Although these respiratory pathogen neuraminidases function in a similar environment, it remains unclear if these enzymes use similar mechanisms for sialic acid cleavage. Here, we compared the enzymatic properties of neuraminidases from two influenza A subtypes (N1 and N2) and the pneumococcal strain TIGR4 (NanA, NanB, and NanC). Insect cell-produced N1 and N2 tetramers exhibited calcium-dependent activities and stabilities that varied with pH. In contrast, E. coli-produced NanA, NanB, and NanC were isolated as calcium insensitive monomers with stabilities that were more resistant to pH changes. Using a synthetic substrate (MUNANA), all neuraminidases showed similar pH optimums (pH 6-7) that were primarily defined by changes in catalytic rate rather than substrate binding affinity. Upon using a multivalent substrate (fetuin sialoglycans), much higher specific activities were observed for pneumococcal neuraminidases that contain an additional lectin domain. In virions, N1 and especially N2 also showed enhanced specific activity toward fetuin that was lost upon the addition of detergent, indicating the sialic acid-binding capacity of neighboring hemagglutinin molecules likely contributes to catalysis of natural multivalent substrates. These results demonstrate that influenza and pneumococcal neuraminidases have evolved similar yet distinct strategies to optimize their catalytic activity.


Asunto(s)
Virus de la Influenza A , Ácido N-Acetilneuramínico , Neuraminidasa , Calcio/metabolismo , Catálisis , Escherichia coli/enzimología , Ácido N-Acetilneuramínico/metabolismo , Neuraminidasa/metabolismo , Streptococcus pneumoniae/enzimología , Virus de la Influenza A/enzimología , Animales , Línea Celular
15.
ACS Synth Biol ; 12(2): 432-445, 2023 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-36716395

RESUMEN

Reverse genetics (RG) systems have been instrumental for determining the molecular aspects of viral replication, pathogenesis, and for the development of therapeutics. Here, we demonstrate that genes encoding the influenza surface antigens hemagglutinin and neuraminidase have varying stability when cloned into a common RG plasmid and transformed into Escherichia coli. Using GFP as a reporter, we demonstrate that E. coli expresses the target genes in the RG plasmid at low levels. Incorporating lac operators or a transcriptional terminator into the plasmid reduced expression and stabilized the viral genes to varying degrees. Sandwiching the viral gene between two lac operators provided the largest contribution to stability and we confirmed the stabilization is Lac repressor-dependent and crucial for subsequent plasmid propagations in E. coli. Viruses rescued from the lac operator-stabilized plasmid displayed similar kinetics and titers to the original plasmid in two different viral backbones. Together, these results indicate that silencing transcription from the plasmid in E. coli helps to maintain the correct influenza gene sequence and that the lac operator addition does not impair virus production. It is envisaged that sandwiching DNA segments between lac operators can be used for reducing DNA segment instability in any plasmid that is propagated in E. coli which express the Lac repressor.


Asunto(s)
Escherichia coli , Gripe Humana , Humanos , Escherichia coli/genética , Escherichia coli/metabolismo , Represoras Lac/genética , Genética Inversa , Plásmidos/genética , Operón Lac
16.
ACS Infect Dis ; 9(1): 33-41, 2023 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-36455156

RESUMEN

Sialidases or neuraminidases are sialic-acid-cleaving enzymes that are expressed by a broad spectrum of organisms, including pathogens. In nature, sialic acids are monosaccharides with diverse structural variations, but the lack of novel probes has made it difficult to determine how sialic acid modifications impact the recognition by sialidases. Here, we used a chemoenzymatic synthon strategy to generate a set of α2-3- and α2-6-linked sialoside probes that contain 7-N-acetyl or 7,9-di-N-acetyl sialic acid as structure mimics for those containing the less stable naturally occurring 7-O-acetyl- or 7,9-di-O-acetyl modifications. These probes were used to compare the substrate specificity of several sialidases from different origins. Our results show that 7-N-acetyl sialic acid was readily cleaved by neuraminidases from H1N1 and H3N2 influenza A viruses, but not by sialidases of human or bacterial origin, thereby indicating that the influenza enzymes possess a distinctive and more promiscuous substrate binding pocket.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Humanos , Ácido N-Acetilneuramínico/metabolismo , Virus de la Influenza A/metabolismo , Neuraminidasa , Subtipo H3N2 del Virus de la Influenza A/metabolismo , Subtipo H1N1 del Virus de la Influenza A/metabolismo , Ácidos Siálicos/química , Ácidos Siálicos/metabolismo
17.
J Neural Eng ; 20(1)2023 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-36535037

RESUMEN

Objective.Although electrical vagus nerve stimulation has been shown to augment parasympathetic control of the heart, the effects of electrical conduction block have been less rigorously characterized. Previous experiments have demonstrated that direct current (DC) nerve block can be applied safely and effectively in the autonomic system, but additional information about the system dynamics need to be characterized to successfully deploy DC nerve block to clinical practice.Approach.The dynamics of the heart rate (HR) from DC nerve block of the vagus nerve were measured by stimulating the vagus nerve to lower the HR, and then applying DC block to restore normal rate. DC block achieved rapid, complete block, as well as partial block at lower amplitudes.Main Results. Complete block was also achieved using lower amplitudes, but with a slower induction time. The time for DC to induce complete block was significantly predicted by the amplitude; specifically, the amplitude expressed as a percentage of the current required for a rapid, 60 s induction time. Recovery times after the cessation of DC block could occur both instantly, and after a significant delay. Both blocking duration and injected charge were significant in predicting the delay in recovery to normal conduction.Significance. While these data show that broad features such as induction and recovery can be described well by the DC parameters, more precise features of the HR, such as the exact path of the induction and recoveries, are still undefined. These findings show promise for control of the cardiac autonomic nervous system, with potential to expand to the sympathetic inputs as well.


Asunto(s)
Estimulación del Nervio Vago , Nervio Vago , Ratas , Animales , Frecuencia Cardíaca/fisiología , Nervio Vago/fisiología , Corazón/inervación , Corazón/fisiología , Estimulación del Nervio Vago/métodos
18.
Pediatr Infect Dis J ; 42(1): 43-46, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36201671

RESUMEN

INTRODUCTION: Treating recurrent multidrug resistant (MDR) urosepsis in pediatric transplant recipients can be challenging. Particularly when antibiotics fail to prevent future occurrence and the nidus is seemingly undiscoverable. While there is an increasing amount of data on phage therapy, to our knowledge, there are no published cases involving pediatric renal transplant recipients. Therefore, we present a challenging clinical case in which phage therapy was used in a pediatric renal transplant recipient who developed recurrent MDR urosepsis with an unclear source. CASE PRESENTATION: Our patient was a 17-year-old female who initially developed urosepsis caused by extended-spectrum ß-lactamase (ESBL) Escherichia coli , while being treated with an immunosuppressant regimen because of kidney rejection secondary to poor immunosuppression therapy compliance. She was admitted to our hospital intermittently for 4 months with 4 episodes of urosepsis caused by ESBL E. coli . She received multiple courses of antibiotics (mainly ertapenem) and underwent a fecal material transplant to eradicate her ESBL E. coli colonized gastrointestinal tract. Because of recurrent development of urosepsis after antibiotic treatment, she later underwent treatment with a phage cocktail consisting of 2 isolate-specific phages. After a prolonged antibiotic course and subsequent 3-week intravenous phage treatment, she had no ESBL E. coli in her urinary cultures for 4 years post-treatment. DISCUSSION: This case highlights the challenges of treating recurrent ESBL E. coli infections in a pediatric renal transplant patient and provides evidence that phage therapy may prove useful in such cases.


Asunto(s)
Trasplante de Riñón , Terapia de Fagos , Humanos , Niño , Adolescente , Escherichia coli , Antibacterianos/uso terapéutico , Trasplante de Riñón/efectos adversos
19.
Artículo en Inglés | MEDLINE | ID: mdl-36516105

RESUMEN

Introduction: In the last decade, the market for Cannabidiol (CBD) has grown to become a near $2 billion dollar industry in the United States alone. This growth can be attributed to a growing social acceptance of marijuana, a more detailed understanding of many health benefits attributed to cannabinoids, and the low cost and wide availibility of hemp-derived cannabinoids. Due to the complex legal histories of marijuana and cannabinoids, the stability and safety of CBD is still an area of interest as research has been restricted globally. Conversion of CBD to its psychoactive isomers, most notably delta-9-Tetrahydrocannabinol (Δ9-THC), presents a significant safety issue for consumers and producers of CBD products. Methods: Previous studies investigating the stability of CBD have focused mainly on replicating conditions experienced during long-term storage at room temperature or lower. Here, we report the thermal stability of CBD at 175°C. Dynamic 1H-NMR experiments and computational electronic structure calculations were used to characterize possible reaction paths from CBD to THC. Results: After 30 minutes of heating, Δ9-THC was produced in detectable amounts in aerobic and anaerobic conditions without an acid catalyst. Conclusions: Our findings support an energetically feasible reaction route that is favorable due to both an increase in phenol acidity at high temperatures and the presence of intramolecular OH-π hydrogen bonding.

20.
iScience ; 25(12): 105607, 2022 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-36452909

RESUMEN

All-organic, flexible, and body-compatible loudspeakers have become increasingly attractive for wearable electronics. Due to their remarkable piezoelectric response, ferroelectrets are suitable for loudspeakers. Two distinct kinds of ultrathin ferroelectrets, including cellular polypropylene films and expanded polytetrafluoroethylene (ePTFE) films, were combined with three different types of electrodes ((Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS))-coated fabrics, PEDOT:PSS direct coating, and sputter-coated Au/Pd) for study regarding their frequency-dependent sound intensity and radiation directivity. Among the loudspeakers investigated, the all-fabric loudspeakers with ePTFE ferroelectret and PEDOT:PSS-coated spandex electrodes have a higher frequency dependency. Loudspeakers equipped with PEDOT:PSS-coated spandex electrodes are less angle dependent compared to other loudspeakers evaluated. Moreover, the soft loudspeaker constituted of an all-organic FEP(fluorinated-ethylene-propylene)-ePTFE-based ferroelectret and PEDOT:PSS-coated fabrics presented in this paper is easy to integrate with clothes and has a higher thermal stability. It is naturally compatible with the human body and a competitive candidate for future developments of all-organic loudspeakers for wearable electronic systems.

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