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1.
Chem Biodivers ; : e202401161, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39073007

RESUMO

In this study, essential oils and waste hydrosols of leaves of Ocimum tenuiflorum in four different geographical locations were extracted by hydrodistillation method and using gas chromatography / mass spectrometry (GC/MS) for chemical composition analysis. All four essential oil samples contained the main components (E)-ß-caryophyllene (27.8-49.0%), trans-ß-elemene (20.3-37.1%) and eugenol (9.0-44.0%). Three of the four hydrosol samples had eugenol in absolute content (94.5-98.6%), while the remaining hydrosol sample had two main components, elemicin (77.8%) and eugenol (14.2%). Essential oils and hydrosols demonstrated larvicidal activities against four important disease-transmitting mosquito species including Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and Culex fuscocephala with 24-h LC50 values in the range 15.42-56.01 µg/mL and 53.88-97.80 µg/mL for the essential oils and the hydrosols, respectively. Essential oils and hydrosols strongly inhibited the acetylcholinesterase (AChE) enzyme of electric eels with IC50 values in the range of 25.35-107.19 µg/mL. Microemulsion (ME) can be considered as a sustainable pesticide formulation over 300 days and has improved larvicidal activity compared to free essential oil. The O. tenuiflorum in Vietnam can be considered a low-cost source of eugenol, botanical pesticides that control disease-transmitting mosquitoes, as well as having therapeutic potential to be further investigated.

2.
PLoS Negl Trop Dis ; 18(7): e0012334, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39074158

RESUMO

Prophylactic drugs against dengue are currently under development. In this study, we explored how such prophylactic approaches might affect dengue cases in four communes of Nha Trang City, Vietnam. A community level dengue transmission survey indicated high levels of previous exposure to dengue (89.7%; 95% CI: 87.2,92.0). We fitted a spatially explicit model to an observed outbreak and simulated likely effectiveness of Case-Area Targeted Interventions (CATI) and One-Time Mass Distribution (OTMD) of drug and vector control strategies. Increasing the radius and effectiveness and decreasing delay of CATI was most effective, with drugs being more effective in averting dengue cases than vector control. Using an OTMD approach early in the outbreak required the least number of treatments to avert a case, suggesting that OTMD strategies should be considered as pre-emptive rather than reactive strategies. These findings show that pre-emptive interventions can substantially reduce the burden of dengue outbreaks in endemic settings.

3.
Acad Radiol ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39013736

RESUMO

RATIONALE AND OBJECTIVES: To determine the potential of large language models (LLMs) to be used as tools by radiology educators to create radiology board-style multiple choice questions (MCQs), answers, and rationales. METHODS: Two LLMs (Llama 2 and GPT-4) were used to develop 104 MCQs based on the American Board of Radiology exam blueprint. Two board-certified radiologists assessed each MCQ using a 10-point Likert scale across five criteria-clarity, relevance, suitability for a board exam based on level of difficulty, quality of distractors, and adequacy of rationale. For comparison, MCQs from prior American College of Radiology (ACR) Diagnostic Radiology In-Training (DXIT) exams were also assessed using these criteria, with radiologists blinded to the question source. RESULTS: Mean scores (±standard deviation) for clarity, relevance, suitability, quality of distractors, and adequacy of rationale were 8.7 (±1.4), 9.2 (±1.3), 9.0 (±1.2), 8.4 (±1.9), and 7.2 (±2.2), respectively, for Llama 2; 9.9 (±0.4), 9.9 (±0.5), 9.9 (±0.4), 9.8 (±0.5), and 9.9 (±0.3), respectively, for GPT-4; and 9.9 (±0.3), 9.9 (±0.2), 9.9 (±0.2), 9.9 (±0.4), and 9.8 (±0.6), respectively, for ACR DXIT items (p < 0.001 for Llama 2 vs. ACR DXIT across all criteria; no statistically significant difference for GPT-4 vs. ACR DXIT). The accuracy of model-generated answers was 69% for Llama 2 and 100% for GPT-4. CONCLUSION: A state-of-the art LLM such as GPT-4 may be used to develop radiology board-style MCQs and rationales to enhance exam preparation materials and expand exam banks, and may allow radiology educators to further use MCQs as teaching and learning tools.

4.
Data Brief ; 55: 110630, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39006346

RESUMO

This dataset explores the perception of happiness and job satisfaction among Vietnamese general school teachers and administrators (principals and vice-principles) in implementing a new curriculum. This study uses SPSS Statistics 26.0 and Exel to analyze data on the opinions of 782 general school teachers and administrators (principles and vice-principles) about satisfaction and happiness at work and influencing factors such as gender, age, experience, income, and workplace, workplaces, difficulties, sources of support when implementing new programs. This dataset contributes to a better understanding of the factors influencing educators' well-being and job satisfaction in the context of curriculum change, providing insights into educational policy and practice in Vietnam and beyond.

5.
Euro Surveill ; 29(28)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38994602

RESUMO

Carbapenem-resistant Acinetobacter baumannii (CRAb) is an important pathogen causing serious nosocomial infections. We describe an outbreak of CRAb in an intensive care unit in the Netherlands in 2021. During an outbreak of non-resistant A. baumannii, while infection control measures were in place, CRAb isolates carrying highly similar bla NDM-1 - and tet(x3)-encoding plasmids were isolated from three patients over a period of several months. The chromosomal and plasmid sequences of the CRAb and non-carbapenemase-carrying A. baumannii isolates cultured from patient materials were analysed using hybrid assemblies of short-read and long-read sequences. The CRAb isolates revealed that the CRAb outbreak consisted of two different strains, carrying similar plasmids. The plasmids contained multiple antibiotic resistance genes including the tetracycline resistance gene tet(x3), and the bla NDM-1 and bla OXA-97 carbapenemase genes. We determined minimal inhibitory concentrations (MICs) for 13 antibiotics, including the newly registered tetracycline antibiotics eravacycline and omadacycline. The CRAb isolates showed high MICs for tetracycline antibiotics including eravacycline and omadacycline, except for minocycline which had a low MIC. In this study we show the value of sequencing multidrug-resistant A. baumannii for outbreak tracking and guiding outbreak mitigation measures.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Infecção Hospitalar , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , Tetraciclinas , beta-Lactamases , Acinetobacter baumannii/genética , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/enzimologia , Humanos , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/epidemiologia , Tetraciclinas/farmacologia , Antibacterianos/farmacologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/epidemiologia , beta-Lactamases/genética , Países Baixos/epidemiologia , Farmacorresistência Bacteriana Múltipla/genética , Plasmídeos/genética , Surtos de Doenças , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Unidades de Terapia Intensiva
7.
Cureus ; 16(5): e60458, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38883043

RESUMO

Introduction The management of maxillofacial trauma can be challenging in different unique clinical presentations. While maxillofacial fractures vary in location based on the mechanism of injury, the mandibular fracture is noted to be one of the most common facial fractures. The objective of this study was to explore the differences in injury patterns, outcomes, and demographics of isolated traumatic mandibular fractures between incarcerated and general populations. Methods This retrospective study analyzed consecutive patients presenting for trauma care from January 1, 2010, to December 31, 2020, at the Arrowhead Regional Medical Center (ARMC). Patients 18 years and older were included in this study. Patients diagnosed with mandibular fracture as the primary diagnosis at admission and discharge were identified using the International Classification of Disease, Ninth and Tenth Revision (ICD-9, ICD-10) Code. Patient demographics were extracted from their electronic medical records and included race, marital status, and insurance status. Results A total of 1080 patients with confirmed mandibular fractures were included in the final analysis. Among these patients, 87.5% (n=945) were males, 40% (n=432) of the patients were Hispanic, and the average age was 31.55 years old. The most common mechanism of injury was blunt trauma secondary to assault. Compared to the general population with mandibular fracture, the incarcerated patients with mandibular fracture were more likely to be males (96.1% vs 86.1% for incarcerated population vs. general population respectively, p=0.0005). No other variables were statistically different between these two groups. Conclusion The evidence from this study suggests that the patterns, outcomes, and demographics of mandibular fracture in both incarcerated and general populations are similar.

8.
Am J Prev Med ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936681

RESUMO

INTRODUCTION: Quantifying the impact of smoking on life expectancy and the potential benefits of smoking cessation is crucial for motivating people who smoke to quit. While previous studies have attempted to estimate these effects, they were conducted more than a decade ago and did not include a significant demographic, people over 65 years old who smoke. METHODS: Mortality rates by age and smoking status were calculated using mortality relative risks derived from Cancer Prevention Study II, 2018 National Health Interview Survey smoking prevalence data, 2018 U.S. population census data, and 2018 U.S. mortality rates. Subsequently, life tables by smoking status-never, current, and former-were constructed. Life expectancies for all three smoking statuses, including those of individuals who had quit smoking at various ages ranging from 35 to 75, were then compared. Additionally, probability distributions of years lost due to smoking and years gained by quitting smoking at different ages were generated. Analyses were conducted in 2023. RESULTS: Compared to people who never smoked, those who smoke currently, aged 35, 45, 55, 65, or 75 years, and who have smoked throughout adulthood until that age, will lose, on average, 9.1, 8.3, 7.3, 5.9, and 4.4 years of life, respectively, if they continue to smoke for the rest of their lives. However, if they quit smoking at each of these ages, they will avoid an average loss of 8.0, 5.6, 3.4, 1.7, and 0.7 years. The chances of gaining at least 1 year of life among those who quit at age 65 and 75 are 23.4% and 14.2%, respectively. CONCLUSIONS: Quitting smoking early will avoid most years otherwise lost due to smoking. Even those who quit at ages 65 and above can still meaningfully increase their life expectancy.

9.
Med Mycol ; 62(6)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935909

RESUMO

The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal pathogen priority list. This systematic review aimed to evaluate the epidemiology and impact of infections caused by Talaromyces marneffei, Coccidioides species, and Paracoccidioides species. PubMed and Web of Sciences databases were searched to identify studies published between 1 January 2011 and 23 February 2021 reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 25, 17, and 6 articles were included for T. marneffei, Coccidioides spp. and Paracoccidioides spp., respectively. Mortality rates were high in those with invasive talaromycosis and paracoccidioidomycosis (up to 21% and 22.7%, respectively). Hospitalization was frequent in those with coccidioidomycosis (up to 84%), and while the duration was short (mean/median 3-7 days), readmission was common (38%). Reduced susceptibility to fluconazole and echinocandins was observed for T. marneffei and Coccidioides spp., whereas >88% of T. marneffei isolates had minimum inhibitory concentration values ≤0.015 µg/ml for itraconazole, posaconazole, and voriconazole. Risk factors for mortality in those with talaromycosis included low CD4 counts (odds ratio 2.90 when CD4 count <200 cells/µl compared with 24.26 when CD4 count <50 cells/µl). Outbreaks of coccidioidomycosis and paracoccidioidomycosis were associated with construction work (relative risk 4.4-210.6 and 5.7-times increase, respectively). In the United States of America, cases of coccidioidomycosis increased between 2014 and 2017 (from 8232 to 14 364/year). National and global surveillance as well as more detailed studies to better define sequelae, risk factors, outcomes, global distribution, and trends are required.


Assuntos
Antifúngicos , Coccidioides , Paracoccidioides , Talaromyces , Organização Mundial da Saúde , Talaromyces/isolamento & purificação , Talaromyces/classificação , Talaromyces/efeitos dos fármacos , Humanos , Paracoccidioides/isolamento & purificação , Paracoccidioides/efeitos dos fármacos , Paracoccidioides/classificação , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Coccidioides/isolamento & purificação , Coccidioides/classificação , Coccidioides/efeitos dos fármacos , Micoses/epidemiologia , Micoses/microbiologia , Micoses/mortalidade , Paracoccidioidomicose/epidemiologia , Paracoccidioidomicose/microbiologia , Paracoccidioidomicose/tratamento farmacológico , Coccidioidomicose/epidemiologia , Coccidioidomicose/microbiologia , Testes de Sensibilidade Microbiana
10.
Asian J Neurosurg ; 19(1): 82-86, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38751397

RESUMO

Staphylococcus aureus is found in the normal skin and mucosa of approximately 30% of healthy populations and is the most common pathogen in human disease associated with bacteria. They are divided into methicillin-sensitive S . aureus (MSSA) and methicillin-resistant S. aureus (MRSA). The S. aureus strains carrying the Panton-Valentine leukocidin genes (SA-PVL) were initially believed to belong to the MRSA group; however, recent reports showed they also belonged to the MSSA group (MSSA-PVL). SA-PVL is common in skin and soft-tissue infections but rare in musculoskeletal infections, especially in spondylodiscitis. We are reporting a case suffering from cervical spondylodiscitis and epidural abscess associated with MSSA carrying the Panton-Valentine leukocidin genes.

11.
RSC Adv ; 14(20): 14263-14277, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38690114

RESUMO

The corrosion of metals is still a huge challenge for various industries, and the pursuit of effective treatments ensures environmental sustainability. In this study, we utilized Chiquita banana sap-water extract (BSWE) to prevent mild steel from electrochemical corrosion in a 0.1 M HCl at room temperature. Corrosion resistance was assessed using various electrochemical methodologies, combining with surface characterization techniques. The results showed a high level of effectiveness when the corrosion current density decreased from 3292.67 µA cm-2 (for the sample immerged in the blank solution) to 187.33 µA cm-2 after 24 hours of immersion in the solution containing BSWE at a 2000 ppm concentration, equivalent to corrosion efficiency of 94.32%. Surface characterization revealed diminished corrosion on the inhibited steel surface due to the formation of a protective layer. X-ray photoelectron spectroscopy results demonstrated the presence of BSWE ingredients combining with iron oxides and hydroxides to form a smooth protective layer. Furthermore, theoretical calculations also indicated that the addition of BSWE can reduce steel surface damage when exposing to corrosive environment. The inhibitor based on banana sap extract can be referred to as a sustainable protective coating since it is biodegradable, abundantly available in banana plants and free of other harmful substances.

12.
Nat Prod Res ; : 1-10, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38600840

RESUMO

This phytochemistry investigation on the trunk of Morus alba L. resulted in the isolation of three triterpenoids, including a new gammacerane triterpenoid - morusacerane (1); along with two known compounds of betulinic acid (2) and ursolic acid (3). The structure elucidation was thoroughly conducted based on 1D, 2D-NMR and HRESIMS spectra, followed by a comparison with existing literatures. The evaluation on α-glucosidase inhibitory exhibited the great potential of the application of these isolated compounds in diabetes treatments. The results show that morusacerane (1), betulinic acid (2), and ursolic acid (3) demonstrate the strong inhibitory with the IC50 values of 106.1, 11.12, and 7.20 µM, respectively. All of these compounds interacted well with the allosteric site enzyme α-glucosidase MAL32 through H-bonds and hydrophobic interaction.

13.
Cureus ; 16(3): e55792, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38586804

RESUMO

In recent years, there has been an increase in the prevalence of the diagnosis of attention-deficit/hyperactivity disorder (ADHD), a cognitive and behavioral disorder in which individuals present with inattention and impulsivity, in the pediatric population. With an increase in diagnoses, there is also increasing concern regarding overdiagnosis and overtreatment with medications for ADHD. The objective of this study was to map out and compile the recent literature pertaining to alternative therapies (e.g., physical activity, diet, mindfulness, and computer-based interventions) for children and adolescents diagnosed with ADHD in an attempt to reduce or replace the use of pharmacological therapy. This scoping review searched articles from multiple databases (PubMed, ScienceDirect, Web of Science, Directory of Open Access Journals, Scopus, and CINAHL). Using search terms "children with ADHD," "alternative treatment," and "cognitive behavioral therapy," articles were identified that were specific to the research question. The inclusion criteria were patients under the age of 18 with a previous diagnosis of ADHD, no other comorbid illnesses, alternative treatments, and was limited to studies published between 2012 and 2022. After removing duplicates, screening for eligibility criteria, and conducting a critical appraisal of the articles, 16 articles were retained for the final review. The main alternative therapeutic domains that emerged were (1) physical activity, (2) diet, (3) mindfulness, (4) computer-based interventions, and (5) miscellaneous interventions. Seven articles assessed the effect of physical activity on executive and cognitive function in children and adolescents with ADHD. Most findings showed improvement with increased physical activity. Two articles explored the effect of diet on the improvement of ADHD symptoms and reported a positive impact. The two articles that evaluated the effects of mindfulness on ADHD symptoms reported a reduction in ADHD symptoms. Two studies evaluated the use of computer-based interventions as an adjunct treatment in children and adolescents with ADHD; improvements in symptoms were reported. One study each evaluated interventions based on music and nerve stimulation. These showed an improvement in attention, memory, and executive function. With the increasing prevalence of ADHD diagnosis in children and adolescents, alternative and/or adjunctive treatments may be a viable and valuable alternative to pharmaceutical interventions. The findings from this review suggest that multiple non-pharmacological interventions effectively reduce symptoms of ADHD in children and adolescents, including diet, exercise, mindfulness, computer-based interventions, music, and nerve stimulation. While there are implications for alternatives to be used in the future, more research is warranted using larger samples with controlled trials.

14.
JMIR Public Health Surveill ; 10: e50189, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564248

RESUMO

BACKGROUND: The COVID-19 pandemic has underscored the significance of adopting healthy lifestyles to mitigate the risk of severe outcomes and long-term consequences. OBJECTIVE: This study focuses on assessing the prevalence and clustering of 5 unhealthy lifestyle behaviors among Vietnamese adults after recovering from COVID-19, with a specific emphasis on sex differences. METHODS: The cross-sectional data of 5890 survivors of COVID-19 in Vietnam were analyzed from December 2021 to October 2022. To examine the sex differences in 5 unhealthy lifestyle behaviors (smoking, drinking, unhealthy diet, physical inactivity, and sedentary behavior), the percentages were plotted along with their corresponding 95% CI for each behavior. Latent class analysis was used to identify 2 distinct classes of individuals based on the clustering of these behaviors: the "less unhealthy" group and the "more unhealthy" group. We examined the sociodemographic characteristics associated with each identified class and used logistic regression to investigate the factors related to the "more unhealthy" group. RESULTS: The majority of individuals (male participants: 2432/2447, 99.4% and female participants: 3411/3443, 99.1%) exhibited at least 1 unhealthy behavior, with male participants being more susceptible to multiple unhealthy behaviors. The male-to-female ratio for having a single behavior was 1.003, but it escalated to 25 for individuals displaying all 5 behaviors. Male participants demonstrated a higher prevalence of combining alcohol intake with sedentary behavior (949/2447, 38.8%) or an unhealthy diet (861/2447, 35.2%), whereas female participants tended to exhibit physical inactivity combined with sedentary behavior (1305/3443, 37.9%) or an unhealthy diet (1260/3443, 36.6%). Married male participants had increased odds of falling into the "more unhealthy" group compared to their single counterparts (odds ratio [OR] 1.45, 95% CI 1.14-1.85), while female participants exhibited lower odds (OR 0.65, 95% CI 0.51-0.83). Female participants who are underweight showed a higher likelihood of belonging to the "more unhealthy" group (OR 1.11, 95% CI 0.89-1.39), but this was not observed among male participants (OR 0.6, 95% CI 0.41-0.89). In both sexes, older age, dependent employment, high education, and obesity were associated with higher odds of being in the "more unhealthy" group. CONCLUSIONS: The study identified notable sex differences in unhealthy lifestyle behaviors among survivors of COVID-19. Male survivors are more likely to engage in unhealthy behaviors compared to female survivors. These findings emphasize the importance of tailored public health interventions targeting sex-specific unhealthy behaviors. Specifically, addressing unhealthy habits is crucial for promoting post-COVID-19 health and well-being.


Assuntos
COVID-19 , Caracteres Sexuais , Adulto , Feminino , Masculino , Humanos , Análise de Classes Latentes , Estudos Transversais , Pandemias , COVID-19/epidemiologia , Análise por Conglomerados , Estilo de Vida
15.
Osong Public Health Res Perspect ; 15(1): 33-44, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38481048

RESUMO

BACKGROUND: The prevalence of posttraumatic stress disorder (PTSD) has increased, particularly among individuals who have recovered from coronavirus disease 2019 (COVID-19) infection. Health literacy is considered a "social vaccine" that helps people respond effectively to the pandemic. We aimed to investigate the association between long COVID-19 and PTSD, and to examine the modifying role of health literacy in this association. METHODS: A cross-sectional study was conducted at 18 hospitals and health centers in Vietnam from December 2021 to October 2022. We recruited 4,463 individuals who had recovered from COVID-19 infection for at least 4 weeks. Participants provided information about their sociodemographics, clinical parameters, health-related behaviors, health literacy (using the 12-item short-form health literacy scale), long COVID-19 symptoms and PTSD (Impact Event Scale-Revised score of 33 or higher). Logistic regression models were used to examine associations and interactions. RESULTS: Out of the study sample, 55.9% had long COVID-19 symptoms, and 49.6% had PTSD. Individuals with long COVID-19 symptoms had a higher likelihood of PTSD (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.63-2.12; p<0.001). Higher health literacy was associated with a lower likelihood of PTSD (OR, 0.98; 95% CI, 0.97-0.99; p=0.001). Compared to those without long COVID-19 symptoms and the lowest health literacy score, those with long COVID-19 symptoms and a 1-point health literacy increment had a 3% lower likelihood of PTSD (OR, 0.97; 95% CI, 0.96-0.99; p=0.001). CONCLUSION: Health literacy was found to be a protective factor against PTSD and modified the negative impact of long COVID-19 symptoms on PTSD.

17.
Ophthalmol Retina ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38403242

RESUMO

PURPOSE: To examine retinal feature dynamics in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF therapy and the relationship of these features with visual acuity. DESIGN: Post hoc analysis of the phase III, randomized, HAWK nAMD clinical trial. PARTICIPANTS: Participants randomized to the brolucizumab 6 mg or aflibercept 2 mg arms of the trial. METHODS: Spectral-domain OCT scans collected at 4-week intervals were analyzed using an automated machine learning-enhanced segmentation and feature-extraction platform with manual verification. Quantitative volumetric measures of retinal and exudative features were exported at multiple timepoints over 48 weeks. Volatility of exudative features was calculated as the standard deviation of each feature value during the maintenance phase (week 12-48) of treatment. These features were examined for their associations with anatomic and functional outcomes. MAIN OUTCOME MEASURES: Longitudinal intraretinal fluid (IRF) and subretinal fluid (SRF) volume, subretinal hyperreflective material (SHRM) volume, ellipsoid zone (EZ) integrity (EZ-retinal pigment epithelium [RPE] volume/thickness), and correlation with best-corrected visual acuity (BCVA). RESULTS: Intraretinal fluid, SRF, and SHRM demonstrated significant volumetric reduction from baseline with anti-VEGF therapy (P < 0.001 at each timepoint). Ellipsoid zone integrity measures demonstrated significant improvement from baseline (P < 0.001 at each timepoint). Both EZ integrity and SHRM measures correlated significantly with BCVA at all timepoints (EZ-RPE volume: 0.38 ≤ r ≤ 0.47; EZ-RPE central subfield thickness: 0.22 ≤ r ≤ 0.41; SHRM volume: -0.33 ≤ r ≤ -0.44). After treatment initiation, correlations of IRF and SRF volume with BCVA were weak or nonsignificant. Eyes with lower volatility of IRF, SRF, and SHRM volumes during the maintenance phase showed greater improvements in EZ integrity (all P < 0.01) and greater gains in BCVA (all P < 0.01) at week 48 compared with eyes with higher volatility in those exudative parameters. CONCLUSIONS: Quantitative measures of SHRM volume and EZ integrity correlated more strongly with BCVA than retinal fluid volumes during treatment. High volatility of exudative parameters, including SRF, during the maintenance phase of treatment was associated with loss of EZ integrity and BCVA. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

19.
Sci Adv ; 10(9): eadm7605, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38416820

RESUMO

Cerebral perfusion is critical for the early detection of neurological diseases and for effectively monitoring disease progression and treatment responses. Mouse models are widely used in brain research, often under anesthesia, which can affect vascular physiology. However, the impact of anesthesia on regional cerebral blood volume and flow in mice has not been thoroughly investigated. In this study, we have developed a whole-brain perfusion MRI approach by using a 5-second nitrogen gas stimulus under inhalational anesthetics to induce transient BOLD dynamic susceptibility contrast (DSC). This method proved to be highly sensitive, repeatable within each imaging session, and across four weekly sessions. Relative cerebral blood volumes measured by BOLD DSC agree well with those by contrast agents. Quantitative cerebral blood volume and flow metrics were successfully measured in mice under dexmedetomidine and various isoflurane doses using both total vasculature-sensitive gradient-echo and microvasculature-sensitive spin-echo BOLD MRI. Dexmedetomidine reduces cerebral perfusion, while isoflurane increases cerebral perfusion in a dose-dependent manner.


Assuntos
Anestesia , Dexmedetomidina , Isoflurano , Animais , Camundongos , Isoflurano/farmacologia , Dexmedetomidina/farmacologia , Imageamento por Ressonância Magnética/métodos , Hipóxia , Encéfalo/irrigação sanguínea , Perfusão , Circulação Cerebrovascular/fisiologia
20.
Nat Commun ; 15(1): 1640, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388531

RESUMO

THOC6 variants are the genetic basis of autosomal recessive THOC6 Intellectual Disability Syndrome (TIDS). THOC6 is critical for mammalian Transcription Export complex (TREX) tetramer formation, which is composed of four six-subunit THO monomers. The TREX tetramer facilitates mammalian RNA processing, in addition to the nuclear mRNA export functions of the TREX dimer conserved through yeast. Human and mouse TIDS model systems revealed novel THOC6-dependent, species-specific TREX tetramer functions. Germline biallelic Thoc6 loss-of-function (LOF) variants result in mouse embryonic lethality. Biallelic THOC6 LOF variants reduce the binding affinity of ALYREF to THOC5 without affecting the protein expression of TREX members, implicating impaired TREX tetramer formation. Defects in RNA nuclear export functions were not detected in biallelic THOC6 LOF human neural cells. Instead, mis-splicing was detected in human and mouse neural tissue, revealing novel THOC6-mediated TREX coordination of mRNA processing. We demonstrate that THOC6 is required for key signaling pathways known to regulate the transition from proliferative to neurogenic divisions during human corticogenesis. Together, these findings implicate altered RNA processing in the developmental biology of TIDS neuropathology.


Assuntos
Deficiência Intelectual , RNA , Estilbenos , Ácidos Sulfônicos , Humanos , Animais , Camundongos , RNA/metabolismo , Deficiência Intelectual/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Processamento Pós-Transcricional do RNA , Transporte de RNA , Mamíferos/genética , Proteínas Nucleares/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
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