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1.
JMIR Cardio ; 8: e59243, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39250778

RESUMEN

The majority of Black women with hypertension in the United States have smartphones or tablets and use social media, and many use wearable activity trackers and health or wellness apps, digital tools that can be used to support lifestyle changes and medication adherence.


Asunto(s)
Negro o Afroamericano , Hipertensión , Aplicaciones Móviles , Medios de Comunicación Sociales , Humanos , Femenino , Estados Unidos/epidemiología , Hipertensión/epidemiología , Persona de Mediana Edad , Adulto , Propiedad , Monitores de Ejercicio , Teléfono Inteligente , Dispositivos Electrónicos Vestibles , Encuestas y Cuestionarios
2.
Sci Rep ; 14(1): 21031, 2024 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251674

RESUMEN

This retrospective cohort study conducted in Turkey between December 2020 and June 2022 aimed to assess antibiotic use, bacterial co-infections, and the associated factors on mortality in hospitalized patients with mild-to-severe COVID-19. Among the 445 patients, 80% received antibiotics, with fluoroquinolones being the most common choice, followed by beta-lactams and combinations. Various clinical and laboratory parameters, including symptoms, comorbidities, CCI, oxygen requirements, and CRP levels were observed to be elevated in the antibiotic group. Non-survivors had more ICU admissions and longer hospital stays compared to survivors. We conducted a multivariate Cox regression analysis to evaluate factors related to mortality. However, we did not find an association between antibiotic use and mortality [HR 2.7 (95% CI 0.4-20)]. The study identified significant factors associated with an antibiotic prescription, such as CCI (OR 1.6), CRP (OR 2.3), and ICU admission (OR 8.8), (p < 0.05). The findings suggest re-evaluating the necessity of antibiotics in COVID-19 cases based on clinical assessments, focusing on the presence of bacterial infections rather than empirical treatment. Further research is necessary to more accurately identify patients with bacterial co-infections who would benefit from antibiotic treatment.


Asunto(s)
Antibacterianos , Tratamiento Farmacológico de COVID-19 , COVID-19 , Humanos , Turquía/epidemiología , Masculino , Antibacterianos/uso terapéutico , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , COVID-19/mortalidad , COVID-19/epidemiología , Coinfección/tratamiento farmacológico , SARS-CoV-2/aislamiento & purificación , Adulto , Infecciones Bacterianas/tratamiento farmacológico , Resultado del Tratamiento , Unidades de Cuidados Intensivos/estadística & datos numéricos
3.
J Adv Pharm Technol Res ; 15(3): 135-138, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39290537

RESUMEN

Acute pain, moderate-to-severe cancer pain, and persistent malignant pain are all frequently treated with opioids. It is regarded as one of the main tenets of analgesic treatment. The relationship between human opioid sensitivity and genetic polymorphism differences has received little attention up to this point in research. Nonetheless, there is mounting proof that pharmacogenomic diversity could affect how each person reacts to opioids. Finding out how gene polymorphism affects analgesic use is the aim of this investigation, particularly opioids. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards were followed in the preparation of the systematic review approach used in this work. Oxycodone, fentanyl, raclopride, tramadol, ketorolac, morphine, ropivacaine, levobupivacaine, subfentanyl, remifentanil, and nortriptyline were the opioid medications used in the study, which was based on 13 publications. From those articles, we reviewed the impact of gene polymorphism on pain management and drug pharmacokinetics. Based on this systematic review, we concluded that gene polymorphism of gene affects analgesic, specifically opioid mechanisms.

4.
JMIR Hum Factors ; 11: e44662, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39250214

RESUMEN

Background: Reductions in opioid prescribing by health care providers can lead to a decreased risk of opioid dependence in patients. Peer comparison has been demonstrated to impact providers' prescribing habits, though its effect on opioid prescribing has predominantly been studied in the emergency department setting. Objective: The purpose of this study is to describe the development of an enterprise-wide opioid scorecard, the architecture of its implementation, and plans for future research on its effects. Methods: Using data generated by the author's enterprise vendor-based electronic health record, the enterprise analytics software, and expertise from a dedicated group of informaticists, physicians, and analysts, the authors developed an opioid scorecard that was released on a quarterly basis via email to all opioid prescribers at our institution. These scorecards compare providers' opioid prescribing habits on the basis of established metrics to those of their peers within their specialty throughout the enterprise. Results: At the time of this study's completion, 2034 providers have received at least 1 scorecard over a 5-quarter period ending in September 2021. Poisson regression demonstrated a 1.6% quarterly reduction in opioid prescribing, and chi-square analysis demonstrated pre-post reductions in the proportion of prescriptions longer than 5 days' duration and a morphine equivalent daily dose of >50. Conclusions: To our knowledge, this is the first peer comparison effort with high-quality evidence-based metrics of this scale published in the literature. By sharing this process for designing the metrics and the process of distribution, the authors hope to influence other health systems to attempt to curb the opioid pandemic through peer comparison. Future research examining the effects of this intervention could demonstrate significant reductions in opioid prescribing, thus potentially reducing the progression of individual patients to opioid use disorder and the associated increased risk of morbidity and mortality.


Asunto(s)
Analgésicos Opioides , Pautas de la Práctica en Medicina , Humanos , Analgésicos Opioides/uso terapéutico , Registros Electrónicos de Salud , Benchmarking
5.
Elife ; 122024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39239703

RESUMEN

The nearly neutral theory of molecular evolution posits variation among species in the effectiveness of selection. In an idealized model, the census population size determines both this minimum magnitude of the selection coefficient required for deleterious variants to be reliably purged, and the amount of neutral diversity. Empirically, an 'effective population size' is often estimated from the amount of putatively neutral genetic diversity and is assumed to also capture a species' effectiveness of selection. A potentially more direct measure of the effectiveness of selection is the degree to which selection maintains preferred codons. However, past metrics that compare codon bias across species are confounded by among-species variation in %GC content and/or amino acid composition. Here, we propose a new Codon Adaptation Index of Species (CAIS), based on Kullback-Leibler divergence, that corrects for both confounders. We demonstrate the use of CAIS correlations, as well as the Effective Number of Codons, to show that the protein domains of more highly adapted vertebrate species evolve higher intrinsic structural disorder.


Evolution is the process through which populations change over time, starting with mutations in the genetic sequence of an organism. Many of these mutations harm the survival and reproduction of an organism, but only by a very small amount. Some species, especially those with large populations, can purge these slightly harmful mutations more effectively than other species. This fact has been used by the 'drift barrier theory' to explain various profound differences amongst species, including differences in biological complexity. In this theory, the effectiveness of eliminating slightly harmful mutations is specified by an 'effective' population size, which depends on factors beyond just the number of individuals in the population. Effective population size is normally calculated from the amount of time a 'neutral' mutation (one with no effect at all) stays in the population before becoming lost or taking over. Estimating this time requires both representative data for genetic diversity and knowledge of the mutation rate. A major limitation is that these data are unavailable for most species. A second limitation is that a brief, temporary reduction in the number of individuals has an oversized impact on the metric, relative to its impact on the number of slighly harmful mutations accumulated. Weibel, Wheeler et al. developed a new metric to more directly determine how effectively a species purges slightly harmful mutations. Their approach is based on the fact that the genetic code has 'synonymous' sequences. These sequences code for the same amino acid building block, with one of these sequences being only slightly preferred over others. The metric by Weibel, Wheeler et al. quantifies the proportion of the genome from which less preferred synonymous sequences have been effectively purged. It judges a population to have a higher effective population size when the usage of synonymous sequences departs further from the usage predicted from mutational processes. The researchers expected that natural selection would favour 'ordered' proteins with robust three-dimensional structures, i.e., that species with a higher effective population size would tend to have more ordered versions of a protein. Instead, they found the opposite: species with a higher effective population size tend to have more disordered versions of the same protein. This changes our view of how natural selection acts on proteins. Why species are so different remains a fundamental question in biology. Weibel, Wheeler et al. provide a useful tool for future applications of drift barrier theory to a broad range of ways that species differ.


Asunto(s)
Evolución Molecular , Selección Genética , Vertebrados , Animales , Vertebrados/genética , Dominios Proteicos , Codón/genética , Variación Genética , Proteínas Intrínsecamente Desordenadas/genética , Proteínas Intrínsecamente Desordenadas/química
6.
Sci Rep ; 14(1): 21281, 2024 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261582

RESUMEN

Tomato brown rugose fruit virus (ToBRFV) poses a significant threat to tomato production worldwide, prompting extensive research into its genetic diversity, evolutionary dynamics, and adaptive strategies. In this study, we conducted a comprehensive analysis of ToBRFV at the codon level, focusing on codon usage bias, selection pressures, and evolutionary patterns across multiple genes. Our analysis revealed distinct patterns of codon usage bias and selection pressures within the ToBRFV genome, with varying levels of genetic diversity and evolutionary constraints among different genes. We observed a transition/transversion bias of 2.07 across the entire ToBRFV genome, with the movement protein (MP) gene exhibiting the highest transition/transversion bias and SNP density, suggesting potential evolutionary pressures or a higher mutation rate in this gene. Furthermore, our study identified episodic positive selection primarily in the MP gene, highlighting specific codons subject to adaptive changes in response to host immune pressures or environmental factors. Comparative analysis of codon usage bias in the coat protein (CP) and RNA-dependent RNA polymerase (RdRp) genes revealed gene-specific patterns reflecting functional constraints and adaptation to the host's translational machinery. Our findings provide valuable insights into the molecular mechanisms driving ToBRFV evolution and adaptation, with implications for understanding viral pathogenesis, host-virus interactions, and the development of control strategies. Future research directions include further elucidating the functional significance of codon usage biases, exploring the role of episodic positive selection in viral adaptation, and leveraging these insights to inform the development of effective antiviral strategies and crop protection measures.


Asunto(s)
Uso de Codones , Evolución Molecular , Genoma Viral , Solanum lycopersicum , Solanum lycopersicum/virología , Solanum lycopersicum/genética , Selección Genética , Adaptación Fisiológica/genética , Enfermedades de las Plantas/virología , Enfermedades de las Plantas/genética , Codón/genética , Variación Genética
7.
Ecol Evol ; 14(9): e70268, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39263460

RESUMEN

Macropsini is a tribe of Eurymelinae in the family Cicadellidae that is widely distributed worldwide. Still, its taxonomic status has been unstable, and the classification of certain clades at the genus level has been controversial. The aim of this study is to address the patterns and processes that explain the structure and the evolution of the mitogenomes of Macropsini, while contributing to the resolution of systematic issues involving five of their genera. To this task, the mitogenomes of 26 species of the tribe were sequenced and characterized, and their phylogenetic relationships were reconstructed. The results revealed that the nucleotide composition of mitochondrial genes in these 26 species was significantly skewed toward A and T. Codons ending with T or A in relative synonymous codon usage were significantly more prevalent than those ending with C or G. The parity plot, neutrality plot, and correspondence analysis revealed that mutation and selective pressure affect codon usage patterns. In the phylogenetic relationships of the Macropsini, the monophyly of Pedionis and Macropsis was well-supported. Meanwhile, Oncopsis revealed paraphyletic regarding Pediopsoides. In conclusion, this research not only contributes the valuable data to the understanding of the mitogenome of the Macropsini but also provides a reference for future investigations on codon usage patterns, potential adaptive evolution, and the phylogeny of the mitogenome within the subfamily Eurymelinae.

8.
EBioMedicine ; 108: 105326, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39260038

RESUMEN

BACKGROUND: The global spread of the plasmid-mediated mcr (mobilized colistin resistance) gene family presents a significant threat to the efficacy of colistin, a last-line defense against numerous Gram-negative pathogens. The mcr-9 is the second most prevalent variant after mcr-1. METHODS: A dataset of 698 mcr-9-positive isolates from 44 countries is compiled. The historical trajectory of the mcr-9 gene is reconstructed using Bayesian analysis. The effective reproduction number is used innovatively to study the transmission dynamics of this mobile-drug-resistant gene. FINDINGS: Our investigation traces the origins of mcr-9 back to the 1960s, revealing a subsequent expansion from Western Europe to the America and East Asia in the late 20th century. Currently, its transmissibility remains high in Western Europe. Intriguingly, mcr-9 likely emerged from human-associated Salmonella and exhibits a unique propensity for transmission within the Enterobacter. Our research provides a new perspective that this host preference may be driven by codon usage biases in plasmids. Specifically, mcr-9-carrying plasmids prefer the nucleotide C over T compared to mcr-1-carrying plasmids among synonymous codons. The same bias is seen in Enterobacter compared to Escherichia (respectively as their most dominant genus). Furthermore, we uncovered fascinating patterns of coexistence between different mcr-9 subtypes and other resistance genes. Characterized by its low colistin resistance, mcr-9 has used this seemingly benign feature to silently circumnavigate the globe, evading conventional detection methods. However, colistin-resistant Enterobacter strains with high mcr-9 expression have emerged clinically, implying a strong risk of mcr-9 evolving into a global "true-resistance-gene". INTERPRETATION: This study explores the mcr-9 gene, emphasizing its origin, adaptability, and dissemination potential. Given the high mcr-9 expression colistin-resistant strains was observed in clinically the prevalence of mcr-9 poses a significant challenge to drug resistance prevention and control within the One Health framework. FUNDING: This work was partially supported by the National Natural Science Foundation of China (Grant No. 32141001 and 81991533).

9.
Microbes Environ ; 39(3)2024.
Artículo en Inglés | MEDLINE | ID: mdl-39261062

RESUMEN

Although microbial inoculation may be effective for sustainable crop production, detrimental aspects have been argued because of the potential of inoculated microorganisms to behave as invaders and negatively affect the microbial ecosystem. We herein compared the impact of rhizobial inoculation on the soil bacterial community with that of agricultural land-use changes using a 16S rRNA amplicon ana-lysis. Soybean plants were cultivated with and without five types of bradyrhizobial inoculants (Bradyrhizobium diazoefficiens or Bradyrhizobium ottawaense) in experimental fields of Andosol, and the high nodule occupancy (35-72%) of bradyrhizobial inoculants was confirmed by nosZ PCR. However, bradyrhizobial inoculants did not significantly affect Shannon's diversity index (α-diversity) or shifts (ß-diversity) in the bacterial community in the soils. Moreover, the soil bacterial community was significantly affected by land-use types (conventional cropping, organic cropping, and original forest), where ß-diversity correlated with soil chemical properties (pH, carbon, and nitrogen contents). Therefore, the effects of bradyrhizobial inoculation on bacterial communities in bulk soil were minor, regardless of high nodule occupancy. We also observed a correlation between the relative abundance of bacterial classes (Alphaproteobacteria, Gammaproteobacteria, and Gemmatimonadetes) and land-use types or soil chemical properties. The impact of microbial inoculation on soil microbial ecosystems has been exami-ned to a limited extent, such as rhizosphere communities and viability. In the present study, we found that bacterial community shifts in soil were more strongly affected by land usage than by rhizobial inoculation. Therefore, the results obtained herein highlight the importance of assessing microbial inoculants in consideration of the entire land management system.


Asunto(s)
Agricultura , Bacterias , Bradyrhizobium , Glycine max , Microbiota , ARN Ribosómico 16S , Microbiología del Suelo , Suelo , ARN Ribosómico 16S/genética , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Suelo/química , Glycine max/microbiología , Glycine max/crecimiento & desarrollo , Bradyrhizobium/clasificación , Bradyrhizobium/genética , Bradyrhizobium/aislamiento & purificación , Bradyrhizobium/fisiología , Inoculantes Agrícolas/fisiología , Inoculantes Agrícolas/clasificación , ADN Bacteriano/genética , Biodiversidad
10.
BMC Surg ; 24(1): 257, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261888

RESUMEN

BACKGROUND: Workplace-based assessment (WBA) can facilitate evaluation of operative performance; however, implementation of WBA is sometimes unsuccessful. The American Board of Surgery Entrustable Professional Activities WBA project was launched in July 2023. Some programs will face the challenge of re-implementation of a WBA following previous failures. It is unknown what interventions are most effective for WBA re-implementation. Our goal is to identify barriers and facilitators to re-implementing SIMPL, an operative performance WBA. METHODS: The System for Improving and Measuring Procedural Learning (SIMPL) was implemented at our residency in 2018, but usage rates were low. We interviewed residents and faculty to identify barriers to usage and opportunities for improvement. Residents reported that SIMPL usage declined because of several factors, including a low faculty response rate, while some faculty reported not responding because they were unable to login to the app and because usage was not mandated. We then re-implemented SIMPL using a plan based on Kotter's Model of Change. To evaluate impact, we analyzed rates of SIMPL usage when it was first implemented, as well as before and after the date of re-implementation. RESULTS: In September 2022, we re-implemented SIMPL at our program with measures addressing the identified barriers. We found that, in the six months after re-implementation, an average of 145.8 evaluations were submitted by residents per month, compared with 47 evaluations per month at the start of the original implementation and 5.8 evaluations per month just prior to re-implementation. Faculty completed 60.6% of evaluations and dictated feedback for 59.1% of these evaluations, compared with 69.1% at implementation (44% dictated) and 43% prior to re-implementation (53% dictated). CONCLUSIONS: After identifying barriers to implementation of a WBA, we re-implemented it with significantly higher usage by faculty and residents. Future opportunities exist to implement or re-implement assessment tools within general surgery programs. These opportunities may have a significant impact in the setting of national standardization of workplace-based assessment among general surgery residencies.


Asunto(s)
Competencia Clínica , Cirugía General , Internado y Residencia , Cirugía General/educación , Humanos , Evaluación Educacional , Lugar de Trabajo , Educación de Postgrado en Medicina/métodos
11.
Front Public Health ; 12: 1403978, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39220447

RESUMEN

Purpose: As science and technology advance, older people's ability to use smart devices in their daily living is becoming more demanding. This study addresses the increasing use of smartphones by the older adults, who often struggle with technology due to lack of competence. We developed an educational app tailored for older adults users and compare its effectiveness with existing educational videos. Methods: An app was created based on the learning characteristics of the older adults, using the ADDIE model, and compared with traditional video education. It involved six participants aged 65 or older, and convenience sampling method was used, evaluating the app and video through usability assessments and eye tracking. Quantitative and qualitative analyzes were conducted with focus groups under the researcher's control. Results: The app received higher usability scores than the video in content, motivation, and interaction. Eye tracking showed users paid more consistent attention to the app. Conclusion: The smartphone app facilitates learning for the older adults without the constraints of time and place, improving their quality of life and technology skills. Eye tracking can be instrumental in future app development for this demographic.


Asunto(s)
Vida Independiente , Aplicaciones Móviles , Teléfono Inteligente , Humanos , Anciano , Femenino , Masculino , Grupos Focales , Empoderamiento , Anciano de 80 o más Años , Calidad de Vida
12.
mBio ; : e0142924, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39248564

RESUMEN

Limited knowledge is available on the differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibody breadth and T cell differentiation among different COVID-19 sequential vaccination strategies. In this study, we compared the immunogenicity of the third different dose of COVID-19 vaccines, such as mRNA (I-I-M), adenoviral vector (I-I-A), and recombinant protein (I-I-R) vaccines, in terms of the magnitude and breadth of antibody response and differentiation of SARS-CoV-2-specific T and B cells. These studies were performed in the same clinical trial, and the samples were assessed in the same laboratory. IGHV1-69, IGHV3-9, and IGHV4-34 were the dominant B cell receptor (BCR) usages of the I-I-M, I-I-A, and I-I-R groups, respectively; the RBD+ B cell activation capacities were comparable. Additionally, the I-I-R group was characterized by higher numbers of regulatory T cells, circulating T follicular helper cells (cTFH) - cTFH1 (CXRC3+CCR6-), cTFH1-17 (CXRC3+CCR6+), cTFH17 (CXRC3-CCR6+), and cTFH-CM (CD45RA-CCR7+), and lower SMNE+ T cell proliferative capacity than the other two groups, whereas I-I-A showed a higher proportion and number of virus-specific CD4+ T cells than I-I-R, as determined in ex vivo experiments. Our data confirmed different SARS-CoV-2-specific antibody profiles among the three different vaccination strategies and also provided insights regarding BCR usage and T/B cell activation and differentiation, which will guide a better selection of vaccination strategies in the future. IMPORTANCE: Using the same laboratory test to avoid unnecessary interference due to cohort ethnicity, and experimental and statistical errors, we have compared the T/B cell immune response in the same cohort sequential vaccinated by different types of COVID-19 vaccine. We found that different sequential vaccinations can induce different dominant BCR usage with no significant neutralizing titers and RBD+ B-cell phenotype. Recombinant protein vaccine can induce higher numbers of regulatory T cells, circulating TFH (CTFH)1, CTFH17, and CTFH-CM, and lower SMNE+ T-cell proliferative capacity than the other two groups, whereas I-I-A showed higher proportion and number of virus-specific CD4+ T cells than I-I-R. Overall, our study provides a deep insight about the source of differences in immune protection of different types of COVID-19 vaccines, which further improves our understanding of the mechanisms underlying the immune response to SARS-CoV-2.

13.
Encephale ; 2024 Sep 06.
Artículo en Francés | MEDLINE | ID: mdl-39244500

RESUMEN

INTRODUCTION: Cannabis is the most consumed illicit substance in Europe. Although its sale and use remain generally prohibited, European public policies have evolved in recent years by legalizing cannabis for medical use and considering its legalization for recreational use. However, in the literature there are arguments in favor of a particular relationship between cannabis consumption and the development of psychotic symptoms. Thus, since cannabis consumption tends to increase with legalization, the aim of this review was to investigate the impact of the legalization of cannabis for recreational use on the risk of psychosis in regions of the world already concerned. METHOD: A systematic review of the literature was carried out in April 2024 in the PubMed-Medline database according to PRISMA criteria. The sequence of keywords used was as follows: ("Cannabis" [Mesh] or cannabis) AND (("Psychotic Disorders" [Mesh] or Psychotic Disorders) or ("Schizophrenia Spectrum and Other Psychotic Disorders" [Mesh]) or ("Schizophrenia" [Mesh] or Schizophrenia)) AND legal use. The inclusion criteria applied for the selection of articles in this systematic review were: (1) any article investigating the potential impact of the legalization of cannabis for recreational use on the risk of psychosis (any type of psychosis diagnosed according to ICD-9, ICD-10, DSM-4 or DSM-5) by the intermediary of epidemiological (incidence or prevalence) and/or clinical (ambulatory consultations, emergency visits or hospitalizations) criteria, (2) any type of study (cross-sectional, longitudinal, prospective, retrospective, interventional and experimental) with a methodology including a temporal and/or geographic comparison of the risk of psychosis associated with the legalization of cannabis for recreational use with the exception of literature reviews and clinical cases descriptions, (3) absence of limitation for the age of the populations studied and for the date of publication, and (4) articles written in English or French. After evaluation by the two authors of the 160 articles identified, seven studies investigating the impact of the legalization of cannabis for recreational use on the risk of psychosis were included in this systematic literature review. RESULTS: Four of the studies showed no increase in the use of health services for psychosis following the legalization of cannabis for recreational use whereas three other studies highlighted a negative impact of the legalization of cannabis for recreational use on the risk of psychosis. All of these studies were carried out in North America and were characterized by a low level of scientific evidence. CONCLUSION: Given the complexity of assessing the impact of the legalization of cannabis for recreational use on the risk of psychosis, additional investigations through studies of better scientific quality are essential. However, based on the data already available, there is some evidence that there is a potential negative impact on mental health due to the legalization of cannabis for recreational use. In this context, in the event of legalization of cannabis for recreational use it seems essential to recommend lower risk use of cannabis (limit the frequency of use, delay the age of first consumption, control the THC content of products and promote prevention/education). Finally, in order to enable dynamic evolution of public health strategies the establishment of continued monitoring is essential as cannabis legalization evolves.

14.
Eng Life Sci ; 24(9): e202400019, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39233725

RESUMEN

While bioactivity and a favorable safety profile for biotherapeutics is of utmost importance, manufacturability is also worth of consideration to ease the manufacturing process. Manufacturability in the scientific literature is mostly related to stability of formulated drug substances, with limited focus on downstream process-related manufacturability, that is, how easily can a protein be purified. Process-related impurities or biological impurities like viruses and host cell proteins (HCP) are present in the harvest which have mostly acid isoelectric points and need to be removed to ensure patient safety. Therefore, during molecule design, the surface charge of the target molecule should preferably differ sufficiently from the surface charge of the impurities to enable an efficient purification strategy. In this feasibility study, we evaluated the possibility of improving manufacturability by adapting the surface charge of the target protein. We generated several variants of a GLP1-receptor-agonist-Fc-domain-FGF21-fusion protein and demonstrated proof of concept exemplarily for an anion exchange chromatography step which then can be operated at high pH values with maximal product recovery allowing removal of HCP and viruses. Altering the surface charge distribution of biotherapeutic proteins can thus be useful allowing for an efficient manufacturing process for removing HCP and viruses, thereby reducing manufacturing costs.

15.
JMIR Hum Factors ; 11: e58371, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39241225

RESUMEN

BACKGROUND: As social media platforms gain popularity, their usage is increasingly associated with cyberbullying and body shaming, causing devastating effects. OBJECTIVE: This study aims to investigate the impact of social media on Generation Z users' body image satisfaction. More specifically, it examines the impact of TikTok on body image satisfaction among TikTok users aged between 17 years and 26 years in Indonesia. METHODS: The methodology used mixed-method approaches. Quantitative data were obtained from 507 responses to a questionnaire and analyzed using covariance-based structural equation modeling. Qualitative data were obtained from the interviews of 32 respondents and analyzed through content analysis. RESULTS: This study reveals that upward appearance comparison is influenced by video-based activity and appearance motivation. Conversely, thin-ideal internalization is influenced by appearance motivation and social media literacy. Upward appearance comparisons and thin-ideal internalization comparisons detrimentally impact users' body image satisfaction. CONCLUSIONS: The results of this study are expected to provide valuable insights for social media providers, regulators, and educators in their endeavors to establish a positive and healthy social media environment for users.


Asunto(s)
Imagen Corporal , Satisfacción Personal , Medios de Comunicación Sociales , Humanos , Indonesia , Femenino , Adulto , Masculino , Adolescente , Imagen Corporal/psicología , Encuestas y Cuestionarios , Adulto Joven , Acoso Escolar/psicología
16.
Gene ; 933: 148935, 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39255859

RESUMEN

Monogeneans of the genus Dactylogyrus Diesing, 1850, the largest genus in the family Dactylogyridae, mostly parasitize the gills of cyprinoid hosts; however, only 3 Dactylogyrus' mitochondrial genomes (mitogenomes) are studied so far. The aim of this research is to extend our understanding of the mitogenomes of Dactylogyrus. We sequenced the mitogenomes of D. crucifer and D. zandti isolated from Rutilus rutilus and Abramis brama orientalis in northwest China, and then we compared these mitogenomes with other monogeneans. We used Illumina NovaSeq to sequence the entire mitochondrial genomes of D. crucifer and D. zandti and characterized the mitogenomes to understand the gene structure, gene identity, the secondary structures of the 22 tRNA genes, and relative synonymous codon usage. We used the analytic Bayesian Information and Maximum Likelihood methods to determine their associated phylogenetic trees. The mitogenomes of D. crucifer and D. zandti were 14,403 and 18,584 bp, respectively. Organization and positioning of these genes were in accordance with Dactylogyrus lamellatus and Dactylogyrus tuba. The nucleotide composition of Dactylogyridae was different from other families of Monogenea, and the A+T count of genus Dactylogyrus (54 - 58.4 %) was lower than other genus species of the family Dactylogyridea (63.9 - 78.4 %) in protein-coding genes. Dactylogyrus members displayed a codon usage bias. The relative synonymous codon used by Dactylogyrus was not conserved and was lower than other monogeneans. The codon use patterns of closely-related species isolated from closely-related hosts were identical. Phylogenetic analyses using mitogenomic dataset produced Dactylogyrus isolated from host subfamily Leuciscinae formed a sister-group. Our results contributed significantly to an increased database of mitogenomes, more than 50 %, for Dactylogyrus that may help future studies of mitochondrial genes and codon uses for the analysis of monogenean phylogenetics.

17.
BMC Bioinformatics ; 25(1): 294, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39242990

RESUMEN

Mouse (Mus musculus) models have been heavily utilized in developmental biology research to understand mammalian embryonic development, as mice share many genetic, physiological, and developmental characteristics with humans. New explorations into the integration of temporal (stage-specific) and transcriptional (tissue-specific) data have expanded our knowledge of mouse embryo tissue-specific gene functions. To better understand the substantial impact of synonymous mutational variations in the cell-state-specific transcriptome on a tissue's codon and codon pair usage landscape, we have established a novel resource-Mouse Embryo Codon and Codon Pair Usage Tables (Mouse Embryo CoCoPUTs). This webpage not only offers codon and codon pair usage, but also GC, dinucleotide, and junction dinucleotide usage, encompassing four strains, 15 murine embryonic tissue groups, 18 Theiler stages, and 26 embryonic days. Here, we leverage Mouse Embryo CoCoPUTs and employ the use of heatmaps to depict usage changes over time and a comparison to human usage for each strain and embryonic time point, highlighting unique differences and similarities. The usage similarities found between mouse and human central nervous system data highlight the translation for projects leveraging mouse models. Data for this analysis can be directly retrieved from Mouse Embryo CoCoPUTs. This cutting-edge resource plays a crucial role in deciphering the complex interplay between usage patterns and embryonic development, offering valuable insights into variation across diverse tissues, strains, and stages. Its applications extend across multiple domains, with notable advantages for biotherapeutic development, where optimizing codon usage can enhance protein expression; one can compare strains, tissues, and mouse embryonic stages in one query. Additionally, Mouse Embryo CoCoPUTs holds great potential in the field of tissue-specific genetic engineering, providing insights for tailoring gene expression to specific tissues for targeted interventions. Furthermore, this resource may enhance our understanding of the nuanced connections between usage biases and tissue-specific gene function, contributing to the development of more accurate predictive models for genetic disorders.


Asunto(s)
Transcriptoma , Animales , Ratones , Transcriptoma/genética , Embrión de Mamíferos/metabolismo , Humanos , Desarrollo Embrionario/genética , Uso de Codones/genética
18.
Sleep Adv ; 5(1): zpae046, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39099832

RESUMEN

Study Objectives: The objective of this study was to investigate the association between demographic, clinical, and interface factors and noninvasive ventilation (NIV) usage. Methods: A retrospective cohort analysis of 478 patients prescribed NIV from 2013 to 2021 was performed. Demographic factors, clinical indications for NIV, and interface factors were collected, and linear regression was conducted to evaluate the association between these variables and NIV usage (hour/night). Results: The average usage of the cohort was 6.5 hour/night ±â€…4.6, with an average age of 57 years ±â€…16 and body mass index (BMI) of 40.5kg/m2 ±â€…14.7. The cohort was mostly male (n = 290, 60.6%). The most common indications for NIV prescription were high-pressure requirement for obstructive sleep apnea (HPR, n = 190, 39.7%), neuromuscular disease (NMD, n = 140, 29.3%), and obesity hypoventilation syndrome (OHS, n = 111, 23.2%). A diagnosis of NMD was a significant predictor of higher NIV usage (8.0 ±â€…6.1 hour/night) in multivariate analysis (p = .036). The HPR subcohort had the lowest usage of all indications. Age and BMI did not predict usage. A nasal interface (p < .01) and lower expiratory positive airway pressure (EPAP) setting (p < .001) were associated with increased NIV usage. Conclusions: This study highlights the multifaceted nature of NIV usage. Where demographic factors were not consistent predictors of usage, interface, and clinical indication were associated with usage. These findings highlight that the HPR users are a group at risk of low usage.

19.
J Basic Microbiol ; : e2400289, 2024 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-39099168

RESUMEN

Ranaviruses, members of the genus Ranavirus within the family Iridoviridae, have become a significant concern for amphibian populations globally, along with other cold-blooded vertebrates, due to their emergence as a significant threat. We employed bioinformatics tools to examine the codon usage patterns in 61 DNA pol genes from Ranavirus, Lymphocystivirus, Megalocytivirus, and two unclassified ranaviruses, as no prior studies had been conducted on this topic. The results showed a slight or low level of codon usage bias (CUB) in the DNA pol genes of Ranavirus. Relative synonymous codon usage (RSCU) analysis indicated that the predominant codons favored in Ranavirus DNA pol genes terminate with C or G. Correlation analysis examining nucleotide content, third codon position, effective number of codons (ENC), correspondence analysis (COA), Aroma values, and GRAVY values indicated that the CUB across DNA pol genes could be influenced by both mutation pressure and natural selection. The neutrality plot indicated that natural selection is the primary factor driving codon usage. Furthermore, the analysis of the codon adaptation index (CAI) illustrated the robust adaptability of Ranavirus DNA pol genes to their hosts. Analysis of the relative codon deoptimization index (RCDI) suggested that Ranavirus DNA pol genes underwent greater selection pressure from their hosts. These findings will aid in comprehending the factors influencing the evolution and adaptation of Ranavirus to its hosts.

20.
Vet Res Commun ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39167257

RESUMEN

Peste des petits ruminants virus (PPRV) is an infectious pathogen; causing highly contagious, acute febrile, and economically important disease of small ruminants. The virus is known to have intrinsic ability to adapt new hosts and to cross the species barrier. The incidence of PPR has already been reported in unusual host species such as camels, bovines, and wild animals from spill-over or natural infection. Still, there are elementary gaps in our knowledge of the extent of susceptibility of camel to PPRV and the adaptability of PPRV to camel. The present study delineates the potential role of preferential codon usage patterns responsible for adaptation, host immune evasion, and transmission of PPRV to unusual hosts like old world camel species namely, dromedary and bactrian camel. The results indicate codon usage of the PPRV genome is functioned by an interplay of mutational pressure and natural selection to exhort the adaptation and fitness of PPRV in probable hosts. The indices of natural selection like the relative codon deoptimization index (RCDI) and codon adaptation index (CAI) predict the ability of PPRV to adapt and evolve in camel species. The analysis also depicts the potential role of the CpG depletion mechanism employed by PPRV to evade host adaptive immune response. The report emphasizes the need for a comprehensive national PPR surveillance plan in unusual hosts like camels for the successful implementation of the PPR Global Eradication Programme (PPR- GEP).

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