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1.
Knee Surg Relat Res ; 36(1): 15, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566254

RESUMO

BACKGROUND: Chat Generative Pretrained Transformer (ChatGPT), a generative artificial intelligence chatbot, may have broad applications in healthcare delivery and patient education due to its ability to provide human-like responses to a wide range of patient queries. However, there is limited evidence regarding its ability to provide reliable and useful information on orthopaedic procedures. This study seeks to evaluate the accuracy and relevance of responses provided by ChatGPT to frequently asked questions (FAQs) regarding total knee replacement (TKR). METHODS: A list of 50 clinically-relevant FAQs regarding TKR was collated. Each question was individually entered as a prompt to ChatGPT (version 3.5), and the first response generated was recorded. Responses were then reviewed by two independent orthopaedic surgeons and graded on a Likert scale for their factual accuracy and relevance. These responses were then classified into accurate versus inaccurate and relevant versus irrelevant responses using preset thresholds on the Likert scale. RESULTS: Most responses were accurate, while all responses were relevant. Of the 50 FAQs, 44/50 (88%) of ChatGPT responses were classified as accurate, achieving a mean Likert grade of 4.6/5 for factual accuracy. On the other hand, 50/50 (100%) of responses were classified as relevant, achieving a mean Likert grade of 4.9/5 for relevance. CONCLUSION: ChatGPT performed well in providing accurate and relevant responses to FAQs regarding TKR, demonstrating great potential as a tool for patient education. However, it is not infallible and can occasionally provide inaccurate medical information. Patients and clinicians intending to utilize this technology should be mindful of its limitations and ensure adequate supervision and verification of information provided.

2.
Int J Neurosci ; : 1-6, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38584514

RESUMO

OBJECTIVE: To analyze the risk factors associated with postoperative stroke complications in cardiac surgery. METHODS: A retrospective analysis was conducted on the clinical data of 549 patients who underwent cardiac surgery. Among these patients, 501 did not experience a stroke postoperatively (non-stroke group), while 48 developed a postoperative stroke (stroke group). Patients who experienced a stroke postoperatively were divided into two groups based on the type of surgery: those who underwent surgery with cardiopulmonary bypass (18 patients) and those without cardiopulmonary bypass (30 patients). The clinical characteristics of the two groups of patients with postoperative strokes were compared, and the risk factors influencing the occurrence of postoperative stroke complications in cardiac surgery were analyzed. RESULTS: ① Clinical findings: Cardiopulmonary bypass group had lower cortical infarction rates but higher large-area and bilateral infarction rates compared to the non-cardiopulmonary bypass group (p < 0.05). No significant gender, age, or infarction type differences were observed (p > 0.05). ② Univariate analysis: No significant differences were found in gender, smoking, alcohol, lipids, or glucose levels (p > 0.05). However, age, education, hypertension, diabetes, hypotension, and atrial fibrillation showed significant differences (p < 0.05). ③ Multivariate Logistic regression: Age, education, hypertension, diabetes, hypotension, and atrial fibrillation were independent risk factors for postoperative stroke complications (p < 0.05). CONCLUSION: Cardiopulmonary bypass increases risk of large-area and bilateral strokes; non-bypass surgery associates with cortical strokes. Age, educational level, hypertension, diabetes, postoperative hypotension, and atrial fibrillation are all factors independently associated with the occurrence of postoperative cerebral infarctions in cardiac surgery. Early interventions may reduce postoperative strokes.

3.
PLoS One ; 19(4): e0299703, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38630707

RESUMO

Vascular cognitive impairment (VCI) is the second leading cause of dementia with limited treatment options, characterised by cerebral hypoperfusion-induced white matter rarefaction (WMR). Subcortical VCI is the most common form of VCI, but the underlying reasons for region susceptibility remain elusive. Recent studies employing the bilateral cortical artery stenosis (BCAS) method demonstrate that various inflammasomes regulate white matter injury and blood-brain barrier dysfunction but whether caspase-1 inhibition will be beneficial remains unclear. To address this, we performed BCAS on C57/BL6 mice to study the effects of Ac-YVAD-cmk, a caspase-1 inhibitor, on the subcortical and cortical regions. Cerebral blood flow (CBF), WMR, neuroinflammation and the expression of tight junction-related proteins associated with blood-brain barrier integrity were assessed 15 days post BCAS. We observed that Ac-YVAD-cmk restored CBF, attenuated BCAS-induced WMR and restored subcortical myelin expression. Within the subcortical region, BCAS activated the NLRP3/caspase-1/interleukin-1beta axis only within the subcortical region, which was attenuated by Ac-YVAD-cmk. Although we observed that BCAS induced significant increases in VCAM-1 expression in both brain regions that were attenuated with Ac-YVAD-cmk, only ZO-1 and occludin were observed to be significantly altered in the subcortical region. Here we show that caspase-1 may contribute to subcortical regional susceptibility in a mouse model of VCI. In addition, our results support further investigations into the potential of Ac-YVAD-cmk as a novel treatment strategy against subcortical VCI and other conditions exhibiting cerebral hypoperfusion-induced WMR.


Assuntos
Clorometilcetonas de Aminoácidos , Disfunção Cognitiva , Substância Branca , Animais , Camundongos , Substância Branca/metabolismo , Encéfalo/metabolismo , Caspase 1/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
5.
BMC Prim Care ; 25(1): 127, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654201

RESUMO

BACKGROUND: Considering time-consuming, cost-related limitations of laboratory-based HbA1c testing and follow-up clinic visits for diabetes management, it is important to explore alternative care models which incorporate point-of-care testing for HbA1c to monitor glycaemic control and related management. METHODS: Therefore, we adopted an implementation perspective to conduct one group pre- and post-intervention feasibility pilot assessing feasibility, acceptability and satisfaction with conducting home HbA1c test by patients with type 2 diabetes coupled with telemonitoring and teleconsultations (i.e., the Primary Technology Enhanced Care (PTEC) Home HbA1c Testing (HAT) Programme) in Singaporean primary care setting. The secondary objective was to compare the HbA1c, blood pressure and primary care visits at the end or during intervention, vs. 6 months before. Adult patients with type 2 diabetes with HbA1c ≤ 8% without any diabetes complications and having phone compatibility were recruited. Data was collected via patient self-reports and electronic medical records extraction. While summary statistics and paired t-test were computed for quantitative data, open-ended feedback was analysed using content analysis. RESULTS: A total of 33 participants completed the intervention out of 37 (33/37 = 89%) recruited from 73 eligible (37/73 = 51%). Most were either 51 to 60 years old (46.9%) or more than 60 years (37.5%), with more males (53.1%) and majority Chinese (93.8%). Majority (81.3%) felt that home HbA1c testing was beneficial with most commonly reported benefit of not having a clinic visit. A key finding was the average of diabetes-related visits being significantly lower post-intervention with comparable HbA1c values pre- and post-intervention. The most commonly reported challenge was using Bluetooth to transmit the reading (43.7%), followed by having too many steps to remember (28.1%). While participants reported being overall satisfied with the intervention, only 22% were willing to pay for it. CONCLUSION: Our findings support home HbA1c testing by patients coupled with telemonitoring and teleconsultations. Following are practical recommendations for the implementation scaling phase: offering PTEC HAT Programme to suitable patients who are self-motivated and have adequate digital literacy, provision of adequate educational and training support, sending reminders and exploring enabling manual submission of HbA1c readings considering Bluetooth-related challenges.


Assuntos
Diabetes Mellitus Tipo 2 , Estudos de Viabilidade , Hemoglobinas Glicadas , Atenção Primária à Saúde , Humanos , Projetos Piloto , Hemoglobinas Glicadas/análise , Singapura , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Masculino , Pessoa de Meia-Idade , Feminino , Satisfação do Paciente , Idoso , Telemedicina/métodos , Serviços de Assistência Domiciliar , Testes Imediatos , Adulto
6.
Heliyon ; 10(6): e27461, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38515732

RESUMO

Introduction: Leeches are flesh-eating and bloodsucking parasitic worms. They are being used as a traditional Chinese medicine for centuries in activating blood and dissolving statis, dreging the meridims and tick. Hirudin, an active peptide product present in leech, has blood anticoagulant property and can assist in the treatment of thrombosis and diseases related to blood circulation. The efficacy and potential mechanism of action of leeches in such diseases should be further explored. Materials and methods: First, network pharmacology was used to screen the predicted potential targets of the active constituents of leech and AS. The common targets of the active constituents of leech and AS were obtained using Venn diagram. Further, the drug-active-constituent-target network diagram, protein-protein interaction, and GO and KEGG pathway enrichment analyses were used to construct the active-constituent-AS target-pathway network diagram. Subsequently, the protein-drug molecule docking model was drawn. Finally, the results of network pharmacology were validated using a mouse model of AS. Results: In total, 34 active constituents of leech and 1172 AS-related gene targets were selected, took the drug action targets and potential disease targets to get the common targets, and took the top 10 of degree value as the main active constituents for the treatment of atherosclerosis. There were 89 common targets and 12 core targets. The main targets included MAPK, EGFR, PIK3CB, etc. Potential regulatory pathways included cancer pathways, EGFR tyrosine kinase inhibitor resistance, Rap1 signaling pathway, PPAR signaling pathway, PI3K-Akt signaling pathway, C-type lectin receptor signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. Animal experiments using mouse model of AS confirmed that AS plaques were smaller after treatment with leeches. SRC level was measured using western blotting. Expression of SRC in myocardial tissue was remarkably lower in the mice treated with leech than in the mice from model group fed on high-fat chow. Conclusions: To the best of our knowledge, this is the first study to explore the mechanism of action of the active components of leech in AS prevention. The active components of leeches play a coordinated role in preventing AS through multicomponent, multitarget, and multichannel mechanism of action related to inflammatory response, oxidative stress, and lipid metabolism. This study provided a reference for subsequent cellular and animal experiments.

7.
Nat Commun ; 15(1): 2386, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493205

RESUMO

Charge density waves (CDWs) involved with electronic and phononic subsystems simultaneously are a common quantum state in solid-state physics, especially in low-dimensional materials. However, CDW phase dynamics in various dimensions are yet to be studied, and their phase transition mechanism is currently moot. Here we show that using the distinct temperature evolution of orientation-dependent ultrafast electron and phonon dynamics, different dimensional CDW phases are verified in CuTe. When the temperature decreases, the shrinking of c-axis length accompanied with the appearance of interchain and interlayer interactions causes the quantum fluctuations (QF) of the CDW phase until 220 K. At T < 220 K, the CDWs on the different ab-planes are finally locked with each other in anti-phase to form a CDW phase along the c-axis. This study shows the dimension evolution of CDW phases in one CDW system and their stabilized mechanisms in different temperature regimes.

8.
Int Arch Occup Environ Health ; 97(4): 401-412, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38480609

RESUMO

OBJECTIVE: This study investigates the associations of α1-antitrypsin, inter-α-trypsin inhibitor heavy chain (ITIH4), and 8-isoprostane with lung function in shipyard workers exposed to occupational metal fume fine particulate matter (PM2.5), which is known to be associated with adverse respiratory outcomes. METHODS: A 3-year follow-up study was conducted on 180 shipyard workers with 262 measurements. Personal exposure to welding fume PM2.5 was collected for an 8-h working day. Pre-exposure, post-exposure, and delta (∆) levels of α1-antitrypsin, ITIH4, and 8-isoprostane were determined in urine using enzyme-linked immunosorbent assays. Post-exposure urinary metals were sampled at the beginning of the next working day and analyzed by inductively coupled plasma-mass spectrometry. Lung function measurements were also conducted the next working day for post-exposure. RESULTS: An IQR increase in PM2.5 was associated with decreases of 2.157% in FEV1, 2.806% in PEF, 4.328% in FEF25%, 5.047% in FEF50%, and 7.205% in FEF75%. An IQR increase in PM2.5 led to increases of 42.155 µg/g in ∆α1-antitrypsin and 16.273 µg/g in ∆ITIH4. Notably, IQR increases in various urinary metals were associated with increases in specific biomarkers, such as post-urinary α1-antitrypsin and ITIH4. Moreover, increases in ∆ α1-antitrypsin and ∆ITIH4 were associated with decreases in FEV1/FVC by 0.008% and 0.020%, respectively, and an increase in ∆8-isoprostane resulted in a 1.538% decline in FVC. CONCLUSION: Our study suggests that urinary α1-antitrypsin and ITIH4 could indicate early lung function decline in shipyard workers exposed to metal fume PM2.5, underscoring the need for better safety and health monitoring to reduce respiratory risks.


Assuntos
Exposição Ocupacional , Soldagem , Humanos , Seguimentos , Estudos Prospectivos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Metais , Material Particulado/análise , Pulmão , Biomarcadores/urina
9.
Neuroimage ; 290: 120569, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38461959

RESUMO

Functional near infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI) both measure the hemodynamic response, and so both imaging modalities are expected to have a strong correspondence in regions of cortex adjacent to the scalp. To assess whether fNIRS can be used clinically in a manner similar to fMRI, 22 healthy adult participants underwent same-day fMRI and whole-head fNIRS testing while they performed separate motor (finger tapping) and visual (flashing checkerboard) tasks. Analyses were conducted within and across subjects for each imaging approach, and regions of significant task-related activity were compared on the cortical surface. The spatial correspondence between fNIRS and fMRI detection of task-related activity was good in terms of true positive rate, with fNIRS overlap of up to 68 % of the fMRI for analyses across subjects (group analysis) and an average overlap of up to 47.25 % for individual analyses within subject. At the group level, the positive predictive value of fNIRS was 51 % relative to fMRI. The positive predictive value for within subject analyses was lower (41.5 %), reflecting the presence of significant fNIRS activity in regions without significant fMRI activity. This could reflect task-correlated sources of physiologic noise and/or differences in the sensitivity of fNIRS and fMRI measures to changes in separate (vs. combined) measures of oxy and de-oxyhemoglobin. The results suggest whole-head fNIRS as a noninvasive imaging modality with promising clinical utility for the functional assessment of brain activity in superficial regions of cortex physically adjacent to the skull.


Assuntos
Imageamento por Ressonância Magnética , Espectroscopia de Luz Próxima ao Infravermelho , Adulto , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Hemodinâmica/fisiologia , Crânio
10.
Heliyon ; 10(5): e27112, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449592

RESUMO

Thrombotic complications of atrial fibrillation continue to pose a significant challenge in clinical practice today. Left atrial appendage occlusion (LAAO) has emerged as a promising alternative to oral anticoagulation for high-risk patients with atrial fibrillation. However, despite the potential benefits, there is still the possibility of life-threatening complications such as device dislocation. In this case study, we present a patient who experienced severe hemodynamic disturbances due to the embolization of LAAO device into the left ventricular outflow tract, resulting in a torn mitral valve and secondary massive mitral regurgitation, just 3 hours after the procedure. As a result, emergent surgical intervention was required to remove the device and repair the mitral valve. We also conducted a review of previous studies on the retrieval of dislodged left atrial appendage occluders through surgical procedures. It is crucial to maintain vigilance, foster interdisciplinary collaboration, and respond promptly to ensure the safety and efficacy of LAAO procedures.

11.
Support Care Cancer ; 32(3): 167, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374479

RESUMO

OBJECTIVE: In China, bladder tumors rank first for morbidity and mortality among urological and reproductive system tumors. Total radical cystectomy plus urinary flow conversion is the gold standard for the treatment of muscle-layer invasive bladder cancer. With an increasing number of radical cystectomies each year, the number of patients living with urostomy is growing. After discharge, primary care of urostomy patients is given at home, and high demands are placed on home caregivers due to issues of privacy and the complexity of replacing the urostomy device. This research explored the challenges faced by the family caregivers of urostomy patients. METHODS: We used descriptive qualitative research methods to conduct interviews with twenty-five family caregivers of patients with urostomy. Survey subjects were from five general hospitals. All interviews were recorded, transcribed, and analyzed using thematic analysis. RESULTS: Three critical challenges were identified-confusion, family crisis, and struggle psychology. Within these three themes, six sub-themes were constructed by coders. They were knowledge and skill deficiency, strong insecurities and uncertainties, role conflict, economic burden, emotional overwhelmed and calm acceptance. CONCLUSION: Family caregivers play a critical role in patient care, and especially in urostomy care. Caregiving is associated with significant challenges that hinder the family caregiver's ability to effectively care for the patient, further diminishing the caregiver's quality of life. Therefore, healthcare professionals should consider the challenges faced by family caregivers and take measures to obviate them through education, preparation, and support.


Assuntos
Cuidadores , Neoplasias da Bexiga Urinária , Humanos , Cuidadores/psicologia , Qualidade de Vida , Emoções , Família/psicologia , Pesquisa Qualitativa
12.
Intern Emerg Med ; 19(3): 721-730, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38386096

RESUMO

Acute-on-chronic liver failure (ACLF) implies high short-term mortality rates and usually requires intensive care unit (ICU) admission. Proper prognosis for these patients is crucial for early referral for liver transplantation. The superiority of CLIF-C ACLF score in Asian patients with ACLF admitted to an ICU remains inconclusive when compared to other scoring systems. The purpose of the study is (i) to compare the predictive performance of original MELD, MELD-Lactate, CLIF-C ACLF, CLIF-C ACLF-Lactate, and APACHE-II scores for short-term mortality assessment. (ii) to build and validate a novel scoring system and to compare its predictive performance to that of the original five scores. Two hundred sixty-five consecutive cirrhotic patients with ACLF who were admitted to our ICU were enrolled. The prognostic values for mortality were assessed by ROC analysis. A novel model was developed and internally validated using fivefold cross-validation. Alcohol abuse was identified as the primary etiology of cirrhosis. The AUROC of the five prognostic scores were not significantly superior to each other in predicting 1-month and 3-month mortality. The newly developed prognostic model, incorporating age, alveolar-arterial gradient (A-a gradient), BUN, total bilirubin level, INR, and HE grades, exhibited significantly improved performance in predicting 1-month and 3-month mortality with AUROC of 0.863 and 0.829, respectively, as compared to the original five prognostic scores. The novel ACLF model seems to be superior to the original five scores in predicting short-term mortality in ACLF patients admitted to an ICU. Further rigorous validation is required.


Assuntos
Insuficiência Hepática Crônica Agudizada , Unidades de Terapia Intensiva , Humanos , Insuficiência Hepática Crônica Agudizada/mortalidade , Masculino , Feminino , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Curva ROC , Índice de Gravidade de Doença , Valor Preditivo dos Testes , APACHE
13.
Resusc Plus ; 17: 100562, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38323138

RESUMO

Aims: Human exposure to high-altitude and/or low-temperature areas is increasing and cardiac arrest in these circumstances represents an increasing proportion of all treated cardiac arrests. However, little is known about the performance of automated external defibrillators (AED) in these circumstances. The objective of this study is to assess the functional and electrical features of 6 commercially available AEDs in extreme environments. Methods: Accuracy of shockable rhythm detection, the time required for self-test, rhythm analysis, and capacitor charging, together with total energy, peak voltage, peak current, and phasic duration of defibrillation waveform measured after placing the AEDs in simulated high-altitude, simulated low-temperature, and natural composite high-altitude and low-temperature environment for 30 min, were compared to those measured in the standard environment. Results: All of the shockable rhythms were correctly detected and all of the defibrillation shocks were successfully delivered by the AEDs. However, the time required for self-test, rhythm detection, and capacitor charging was shortened by 1.2% (3 AEDs, maximum 12.4%) in the simulated high-altitude environment, was prolonged by 3.6% (4 AEDs, maximum 40.8%) in the simulated low-temperature environment, and was prolonged by 4.1% (5 AEDs, maximum 52.1%) in the natural environment. Additionally, the total delivered energy was decreased by 2.5% (2 AEDs, maximum 6.8%) in the natural environment. Conclusion: All of the investigated AEDs functioned properly in simulated and natural environments, but a large variation in the functional and electrical feature change was observed. When performing cardiopulmonary resuscitation in extreme environments, the impact of environmental factors may need consideration.

14.
J Med Virol ; 96(2): e29469, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38376919

RESUMO

The mpox outbreak has subdued with fewer reported cases at the present in high-income countries. It is known that mpox virus (MPXV) infection has been epidemic for more than 50 years in African countries. The ancestral MPXV strain has changed into multiple clades, indicating the ongoing evolution of MPXV, which reflects the historical neglect of mpox in Africa, especially after smallpox eradication, and bestows the danger of more severe mpox epidemics in the future. It is thus imperative to continue the development of mpox diagnostics and treatments so we can be prepared in the event of a new mpox epidemic. In this study, we have developed an MPXV detection tool that leverages the recombinase-aid amplification assay by integrating lateral flow strips (RAA-LF) and one-step sample DNA preparation, with visible readout, no need of laboratory instrument, and ready for field deployment. The detection limit reaches 10 copies per reaction. The performance of our RAA-FL assay in diagnosing mpox clinical samples is on par with that of the quantitative polymerase chain reaction (PCR) assay. Taken together, we have developed a point-of-care RAA-LF method of high accuracy and sensitivity, readily deployable for field detection of MPXV. This diagnostic tool is expected to improve and accelerate field- and self-diagnosis, allow timely isolation and treatment, reduce the spread of MPXV, thus effectively mitigate MPXV outbreak in the future.


Assuntos
Vírus da Varíola dos Macacos , Varíola dos Macacos , Humanos , África , Bioensaio , Surtos de Doenças
15.
Cancer Metab ; 12(1): 6, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365771

RESUMO

BACKGROUND: Metastasis is the leading cause of death among prostate cancer (PCa) patients. Obesity is associated with both PCa-specific and all-cause mortality. High-fat diet (HFD) is a risk factor contributing to obesity. However, the association of HFD with PCa metastasis and its underlying mechanisms are unclear. METHODS: Tumor xenografts were conducted by intrasplenic injections. The ability of migration or invasion was detected by transwell assay. The expression levels of RPS27 were detected by QRT-PCR and western blot. RESULTS: The present study verified the increase in PCa metastasis caused by HFD in mice. Bioinformatics analysis demonstrated increased RPS27 in the experimentally induced PCa in HFD mice, indicating that it is an unfavorable prognostic factor. Intrasplenic injections were used to demonstrate that RPS27 overexpression promotes, while RPS27 knockdown significantly reduces, PCa liver metastasis. Moreover, RPS27 inhibition suppresses the effects of HFD on PCa metastasis. Further mRNA sequencing analysis revealed that RPS27 promotes PCa metastasis by selectively enhancing the expression of various genes. CONCLUSION: Our findings indicate that HFD increases the risk of PCa metastasis by elevating RPS27 expression and, subsequently, the expression of genes involved in PRAD progression. Therefore, RPS27 may serve as a novel target for the diagnosis and treatment of metastatic PCa.

16.
medRxiv ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38260438

RESUMO

Phospholipase C isozymes (PLCs) hydrolyze phosphatidylinositol 4,5-bisphosphate into inositol 1,4,5-trisphosphate and diacylglycerol, important signaling molecules involved in many cellular processes. PLCG1 encodes the PLCγ1 isozyme that is broadly expressed. Hyperactive somatic mutations of PLCG1 are observed in multiple cancers, but only one germline variant has been reported. Here we describe three unrelated individuals with de novo heterozygous missense variants in PLCG1 (p.Asp1019Gly, p.His380Arg, and p.Asp1165Gly) who exhibit variable phenotypes including hearing loss, ocular pathology and cardiac septal defects. To model these variants in vivo, we generated the analogous variants in the Drosophila ortholog, small wing (sl). We created a null allele slT2A and assessed the expression pattern. sl is broadly expressed, including in wing discs, eye discs, and a subset of neurons and glia. Loss of sl causes wing size reductions, ectopic wing veins and supernumerary photoreceptors. We document that mutant flies exhibit a reduced lifespan and age-dependent locomotor defects. Expressing wild-type sl in slT2A mutant rescues the loss-of-function phenotypes whereas expressing the variants causes lethality. Ubiquitous overexpression of the variants also reduces viability, suggesting that the variants are toxic. Ectopic expression of an established hyperactive PLCG1 variant (p.Asp1165His) in the wing pouch causes severe wing phenotypes, resembling those observed with overexpression of the p.Asp1019Gly or p.Asp1165Gly variants, further arguing that these two are gain-of-function variants. However, the wing phenotypes associated with p.His380Arg overexpression are mild. Our data suggest that the PLCG1 de novo heterozygous missense variants are pathogenic and contribute to the features observed in the probands.

17.
J Am Nutr Assoc ; : 1-7, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38227813

RESUMO

OBJECTIVE: Benzene is widely recognized as a potential carcinogen. Furthermore, the deficiency of specific nutrients may render individuals more vulnerable to cancer. For instance, ß-cryptoxanthin, which possesses anti-inflammatory, antioxidant, and anticancer properties, has been identified as one such nutrient. Elevated benzene levels and reduced ß-cryptoxanthin levels are reportedly correlated with an augmented susceptibility to cancer. To date, whether these 2 substances are linked with one another in the above correlation is yet to be determined. METHOD: This study included 1358 participants with data on the serum concentration of ß-cryptoxanthin as well as benzene and its derivatives. The data were sourced from the 2003-2004 National Health and Nutrition Examination Survey, a cross-sectional survey of the noninstitutionalized US population. Headspace solid-phase microextraction with gas chromatography and mass spectrometry was used to measure serum benzene and its derivatives, while high-performance liquid chromatography using multiwavelength photodiode-array absorbance detection was employed to quantify serum ß-cryptoxanthin. RESULTS: In this study, male and female participants showed average ß-cryptoxanthin levels of 9.10 ± 6.35 and 9.92 ± 8.95 ug/dL, respectively (p = 0.049). Styrene exhibited the strongest correlation with the change in ß-cryptoxanthin concentration (ß = -3.30, p for trend <0.001) upon comparing highest-quartile participants with those in the lowest quartile, followed by benzene (ß = -2.95, p for trend <0.001), toluene (ß = -2.90, p for trend <0.001), and ethylbenzene (ß = -1.43, p for trend = 0.09). Subgroup analysis by sex displayed a statistically significant negative correlation of ß-cryptoxanthin with benzene, styrene, and toluene in both the unadjusted and multivariate-adjusted models. CONCLUSIONS: The sera of noninstitutionalized US individuals exhibit a negative association of ß-cryptoxanthin levels with benzene and its derivatives. Styrene demonstrates the strongest link with a substantial decline in serum ß-cryptoxanthin levels, followed by benzene, toluene, and ethylbenzene.

18.
BMC Cancer ; 24(1): 41, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183079

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased risk of lung cancer mortality. Nevertheless, little is known about the underlying molecular mechanisms. This research aimed to investigate differentially expressed genes (DEGs) and explore their function in Lewis lung carcinoma (LLC)-bearing mice exposed to chronic intermittent hypoxia (CIH) by transcriptome sequencing. METHODS: Lung cancer tissues in LLC-bearing mice exposed to CIH or normoxia were subjected for transcriptome sequencing to examine DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were employed to explore the function of DEGs. To evaluate the prognostic value of DEGs, the Kaplan-Meier survival analysis in combination with Cox proportional hazard model were applied based on The Cancer Genome Atlas. RESULTS: A total of 388 genes with 207 up-regulated and 181 down-regulated genes were differentially expressed between the CIH and normoxia control groups. Bioinformatics analysis revealed that the DEGs were related to various signaling pathways such as chemokine signaling pathway, IL-17 signaling pathway, TGF-ß signaling pathway, transcriptional misregulation in cancer, natural killer cell mediated cytotoxicity, PPAR signaling pathway. In addition, the DEGs including APOL1, ETFB, KLK8, PPP1R3G, PRL, SPTA1, PLA2G3, PCP4L1, NINJ2, MIR186, and KLRG1 were proven to be significantly correlated with poorer overall survival in lung adenocarcinoma. CONCLUSIONS: CIH caused a significant change of gene expression profiling in LLC-bearing mice. The DEGs were found to be involved in various physiological and pathological processes and correlated with poorer prognosis in lung cancer.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Lewis , Neoplasias Pulmonares , Animais , Camundongos , Neoplasias Pulmonares/genética , Transcriptoma , Processos Neoplásicos , Hipóxia/genética
19.
Neurotherapeutics ; 21(1): e00323, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38244258

RESUMO

Mitochondrial diseases are inherited disorders that impede the mitochondria's ability to produce sufficient energy for the cells. They can affect different parts of the body, notably the brain. Neurological symptoms and epilepsy are prevalent in patients with mitochondrial disorders. The epileptogenicity of mitochondrial disorder is a complex process involving the intricate interplay between abnormal energy metabolism and neuronal activity. Several modalities have been used to detect seizures in different disorders including mitochondrial disorders. EEG serve as the gold standard for diagnosis and localization, commonly complemented by additional imaging modalities to enhance source localization. In the current work, we propose the use of functional near-infrared spectroscopy (fNIRS) to identify the occurrence of epilepsy and seizure in patients with mitochondrial disorders. fNIRS proves an advantageous imaging technique due to its portability and insensitivity to motion especially for imaging infants and children. It has added a valuable factor to our understanding of energy metabolism and neuronal activity. Its real-time monitoring with high spatial resolution supplements traditional diagnostic tools such as EEG and provides a comprehensive understanding of seizure and epileptogenesis. The utility of fNIRS extends to its ability to detect changes in Cytochrome c oxidase (CcO) which is a crucial enzyme in cellular respiration. This facet enhances our insight into the metabolic dimension of epilepsy related to mitochondrial dysfunction. By providing valuable insights into both energy metabolism and neuronal activity, fNIRS emerges as a promising imaging technique for unveiling the complexities of mitochondrial disorders and their neurological manifestations.


Assuntos
Epilepsia , Doenças Mitocondriais , Criança , Lactente , Humanos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Epilepsia/diagnóstico por imagem , Epilepsia/metabolismo , Encéfalo/metabolismo , Convulsões , Doenças Mitocondriais/diagnóstico por imagem
20.
EClinicalMedicine ; 68: 102407, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38235420

RESUMO

Background: The unprecedented global outbreak of mpox in 2022 posed a public health challenge. In addition to the mpox vaccine campaign in the United States (US), community organisations and public health agencies initiated educational efforts to promote sexual risk reduction. This modelling study estimated the impact of the two-dose vaccination campaign and sexual behaviour changes coincident with high-risk group awareness on the mpox epidemic in the US. Methods: We fitted a deterministic, risk-structured SEIARV model to the epidemic curve of reported mpox cases in the US between May 22, 2022 and December 22, 2022. We evaluated the putative effects of the two preventive responses in the US -- vaccination and sexual risk reduction -- at the population-level, by calculating the prevention percentages of cumulative cases compared to the counterfactual scenario without interventions. We performed sensitivity analyses with four parameters: case reporting fidelity, vaccine effectiveness, proportion of asymptomatic cases, and assortative mixing. Findings: Model fitting revealed a basic reproduction number of 3.88 and 0.39 for the high-risk and low-risk populations, respectively, with 71.8% of mpox cases estimated from the high-risk population. A two-dose vaccination campaign, solely, could prevent 21.2% (10.2%-24.1%) of cases, while behaviour changes due to high-risk group awareness alone could prevent 15.4% (14.3%-20.6%). The combination of both measures were synergistic, with the model suggesting that 64.0% (43.8%-69.0%) of US cases were averted that would have otherwise occurred. Interpretation: Our models suggest that the 2022-2023 mpox epidemic in the US was controlled by a combination of two-dose mpox vaccination campaign and high-risk group awareness and sexual risk reduction. Funding: Taiwan Ministry of Education grant #NTU-112L9004, Taiwan National Science and Technology Council grant #MOST-109-2314-B-002-147-MY3 and grant #NSC-112-2314-B-002-216-MY3. SHV was supported, in part, by US National Institutes of Health grant #P30MH062294.

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