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1.
medRxiv ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39281757

RESUMEN

This study examined the relationship between lifestyles (diet, sleep, and physical activity) and glucose responses at a personal level. 36 healthy adults in the Bay Area were monitored for their lifestyles and glucose levels using wearables and continuous glucose monitoring (NCT03919877). Gold-standard metabolic tests were conducted to phenotype metabolic characteristics. Through the lifestyle data (2,307 meals, 1,809 nights, and 2,447 days) and 231,206 CGM readings from metabolically-phenotyped individuals with normoglycemia or prediabetes, we found: 1) eating timing was associated with hyperglycemia, muscle insulin resistance (IR), and incretin dysfunction, whereas nutrient intakes were not; 2) timing of increased activity in muscle IS and IR participants was associated with differential benefits of glucose control; 3) Integrated ML models using lifestyle factors predicted distinct metabolic characteristics (muscle, adipose IR or incretin dysfunction). Our data indicate the differential impact of lifestyles on glucose regulation among individuals with different metabolic phenotypes, highlighting the value of personalized lifestyle modifications.

2.
Sci Rep ; 14(1): 21693, 2024 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-39289449

RESUMEN

Helicobacter pylori can infect most people worldwide to cause hazardous consequences to health; the bacteria could not easily be controlled or disinfected. Toward exploring of innovative biocidal nanoformulations to control H. pylori, broccoli seeds (Brassica oleracea var. italica) mucilage (MBS) was employed for biosynthesizing selenium nanoparticles (MBS/SeNPs), which was intermingled with chitosan nanoparticles (NCT) to generate bioactive nanocomposites for suppressing H. pylori. The MBS could effectually generate and stabilize SeNPs with 13.61 nm mean diameter, where NCT had 338.52 nm mean diameter and positively charged (+ 39.62 mV). The cross-linkages between NCT-MBS-SeNPs were verified via infrared analysis and the nanocomposites from NCT:MBS/SeNPs at 1:2 (T1), 1:1 (T2) and 2:1 (T3) ratios had mean diameters of 204, 132 and 159 nm, respectively. The entire nanomaterials/composites exhibited potent anti- H. pylori activities using various assaying methods; the T2 nanocomposite was the utmost bactericidal agent with 0.08-0.10 mg/L minimal concentration and 25.9-27.3 mm inhibition zones. The scanning microscopy displayed the ability of nanocomposite to attach the bacterial cells, disrupt their membranes, and completely lyse them within 10 h. The NCT/MBS/SeNPs nanocomposites provided effectual innovative approach to control H. pylori.


Asunto(s)
Antibacterianos , Brassica , Quitosano , Helicobacter pylori , Nanocompuestos , Mucílago de Planta , Selenio , Helicobacter pylori/efectos de los fármacos , Quitosano/química , Quitosano/farmacología , Nanocompuestos/química , Selenio/química , Selenio/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Brassica/microbiología , Mucílago de Planta/química , Nanopartículas/química , Pruebas de Sensibilidad Microbiana
3.
Nat Metab ; 6(9): 1712-1735, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39261628

RESUMEN

Glucose, the primary cellular energy source, is metabolized through glycolysis initiated by the rate-limiting enzyme hexokinase (HK). In energy-demanding tissues like the brain, HK1 is the dominant isoform, primarily localized on mitochondria, and is crucial for efficient glycolysis-oxidative phosphorylation coupling and optimal energy generation. This study unveils a unique mechanism regulating HK1 activity, glycolysis and the dynamics of mitochondrial coupling, mediated by the metabolic sensor enzyme O-GlcNAc transferase (OGT). OGT catalyses reversible O-GlcNAcylation, a post-translational modification influenced by glucose flux. Elevated OGT activity induces dynamic O-GlcNAcylation of the regulatory domain of HK1, subsequently promoting the assembly of the glycolytic metabolon on the outer mitochondrial membrane. This modification enhances the mitochondrial association with HK1, orchestrating glycolytic and mitochondrial ATP production. Mutation in HK1's O-GlcNAcylation site reduces ATP generation in multiple cell types, specifically affecting metabolic efficiency in neurons. This study reveals a previously unappreciated pathway that links neuronal metabolism and mitochondrial function through OGT and the formation of the glycolytic metabolon, providing potential strategies for tackling metabolic and neurological disorders.


Asunto(s)
Glucólisis , Hexoquinasa , Mitocondrias , N-Acetilglucosaminiltransferasas , Mitocondrias/metabolismo , Hexoquinasa/metabolismo , Humanos , N-Acetilglucosaminiltransferasas/metabolismo , N-Acetilglucosaminiltransferasas/genética , Animales , Neuronas/metabolismo , Adenosina Trifosfato/metabolismo , Glucosa/metabolismo , Procesamiento Proteico-Postraduccional , Ratones , Fosforilación Oxidativa
4.
Cureus ; 16(8): e67955, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39328707

RESUMEN

BACKGROUND: Rectal malignancy ranks among the most prevalent malignancies in humans. Neoadjuvant chemoradiotherapy (nCRT) is advocated as the standard treatment for locally advanced rectal cancer. In patients who achieve complete clinical response (cCR), successive surgical intervention may result in favorable immediate and long-lasting results; however, it may be associated with decreased quality of life. This study aims to evaluate the incidence of local recurrence in rectal adenocarcinoma between patients who underwent a watch-and-wait approach and those who underwent abdominoperineal resection following the achievement of a cCR after nCRT. METHODS: This is an analytic cohort study that included 68 patients and was conducted in Baghdad Teaching Hospital/Medical City, Baghdad. The data were collected from the 1st of April 2021 to the 1st of October 2023. All patients with stage II and III rectal adenocarcinoma who achieved cCR after receiving nCRT were included in the study. RESULTS: There was no statistically significant difference between the two study groups regarding non-regrowth disease-free survival (p-value = 0.708). Cox-regression multivariate analysis revealed that baseline T stage and serum carcinoembryonic antigen (CEA) were significantly associated with locoregional failure. CONCLUSION: The present study reveals that implementing the watch-and-wait strategy had the benefit of avoiding major surgery, stoma, and their complications without coming at the cost of reduced locoregional recurrence.

5.
Bioorg Chem ; 153: 107843, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39332072

RESUMEN

In this work, additional effort was applied to design new BIBR1532-based analogues with potential inhibitory activity against telomerase and acting as multitarget antitumor candidates to overcome the resistance problem. Therefore, novel substituted N-phenyl-2-((6-phenylpyridazin-3-yl)thio)acetamide candidates (4a-n) were synthesized. Applying the lead optimization strategy of the previously designed compound 8e; compound 4l showed an improved telomerase inhibition of 64.95 % and a superior growth inhibition of 79 % suggesting its potential use as a successful "multitarget-directed drug" for cancer therapy. Accordingly, compound 4l was further selected to evaluate its additional JAK1/STAT3/TLR4 inhibitory potentials. Compound 4l represented a very promising JAK1 inhibitory potential with a 0.46-fold change, compared to that of pacritinib reference standard (0.33-fold change). Besides, it showed a superior STAT3-inhibitory potential with a 0.22-fold change compared to sorafenib (0.33-fold change). Additionally, compound 4l downregulated TLR4 protein expression by 0.81-fold change compared to that of resatorvid (0.29-fold change). Also, molecular docking was performed to investigate the binding mode and affinity of the superior candidate 4l towards the four target receptors (telomerase, JAK1, STAT3, and TLR4). Furthermore, the therapeutic potential of compound 4l as an antitumor agent was additionally explored through in vivo studies involving female mice implanted with Solid Ehrlich Carcinoma (SEC). Remarkably, compound 4l led to prominent reductions in tumor size and mass. Concurrent enhancements in biochemical, hematologic, histopathologic, and immunohistochemical parameters further confirmed the suppression of angiogenesis and inflammation, elucidating additional mechanisms by which compound 4l exerts its anticancer effects.

6.
World J Virol ; 13(3): 96369, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39323451

RESUMEN

BACKGROUND: Chronic hepatitis C (CHC) is a health burden with consequent morbidity and mortality. Liver biopsy is the gold standard for evaluating fibrosis and assessing disease severity and prognostic purposes post-treatment. Noninvasive alternatives for liver biopsy such as transient elastography (TE) and diffusion-weighted magnetic resonance imaging (DW-MRI) are critical needs. AIM: To evaluate TE and DW-MRI as noninvasive tools for predicting liver fibrosis in children with CHC. METHODS: This prospective cross-sectional study initially recruited 100 children with CHC virus infection. Sixty-four children completed the full set of investigations including liver stiffness measurement (LSM) using TE and measurement of apparent diffusion coefficient (ADC) of the liver and spleen using DW-MRI. Liver biopsies were evaluated for fibrosis using Ishak scoring system. LSM and liver and spleen ADC were compared in different fibrosis stages and correlation analysis was performed with histopathological findings and other laboratory parameters. RESULTS: Most patients had moderate fibrosis (73.5%) while 26.5% had mild fibrosis. None had severe fibrosis or cirrhosis. The majority (68.8%) had mild activity, while only 7.8% had moderate activity. Ishak scores had a significant direct correlation with LSM (P = 0.008) and were negatively correlated with both liver and spleen ADC but with no statistical significance (P = 0.086 and P = 0.145, respectively). Similarly, histopathological activity correlated significantly with LSM (P = 0.002) but not with liver or spleen ADC (P = 0.84 and 0.98 respectively). LSM and liver ADC were able to significantly discriminate F3 from lower fibrosis stages (area under the curve = 0.700 and 0.747, respectively) with a better performance of liver ADC. CONCLUSION: TE and liver ADC were helpful in predicting significant fibrosis in children with chronic hepatitis C virus infection with a better performance of liver ADC.

7.
Heliyon ; 10(18): e37790, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39323795

RESUMEN

Background: Saussurea costus (S. costus) is a critically endangered medicinal plant that has been extensively studied for its chemical composition, significance, and therapeutic potential as traditional phytomedicine. This comprehensive review aims to provide a thorough understanding of S. costus, including its biological activities, chemical makeup, and potential therapeutic uses in biotechnology. Objectives: This study investigated the pharmacological properties of S. costus, including its antimicrobial, antioxidant, and antifungal properties, and its usefulness in treating conditions such as thyroid disorders and liver injury. This study also aimed to assess and improve the techniques used to extract bioactive compounds and to develop effective methods for harvesting these compounds from medicinal plants. Methods: This review analyzed the available literature on the phytochemical makeup and bioactivity of S. costus extract using techniques such as molecular docking against SARS-CoV-2 protease, green extraction methods, and phytochemical analysis. Results: This review revealed that S. costus possesses various pharmacological properties, including antimicrobial, antiviral, anti-inflammatory, and anticancer activities. It is effective in combating fungal infections, reducing inflammation, treating cancer, and inhibiting viral replication, and has the potential to control Candida species. Moreover, S. costus has been explored for its capacity to synthesize nanoparticles with antimicrobial properties and for its potential in treating thyroid disorders and liver injury. Recommendations: Despite promising results, additional research is necessary to fully comprehend the benefits of S. costus and validate its effectiveness in clinical settings. Future research should focus on standardized methodologies and rigorous clinical trials to confirm the safety and effectiveness of S. costus in various medical fields as well as further investigate its biotechnological and pharmaceutical applications.

8.
Front Chem ; 12: 1456057, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39324064

RESUMEN

Zinc-phosphate/hydroxyapatite hybrid form (ZP/HP) in core-shell nanostructure was developed and functionalized with both chitosan (CS@ZP/HP) and ß-cyclodextrin (CD@ZP/HP) as bio-composite of enhanced physicochemical and biological properties. These structures were assessed as potential deliveries of 5-fluorouracil, exhibiting enhanced loading, release, and anti-cancer behaviors. The functionalization strongly prompted the loading effectiveness to be 301.3 mg/g (CS@ZP/HP) and 342.8 mg/g (CD@ZP/HP) instead of 238.9 mg/g for ZP/HP. The loading activities were assessed based on the hypotheses of traditional kinetic and isotherm models, alongside the computational variables of the monolayer model with a single energetic site as an advanced isotherm model. The functionalized versions exhibit much greater loading efficacy compared to ZP/HP as a result of the increment in the density of the existing loading sites [Nm(5-Fu) = 78.85 mg/g (ZP/HP), 93.87 mg/g (CS@ZP/HP), and 117.8 mg/g (CD@ZP/HP)]. Furthermore, the loading energies of approximately 40 kJ/mol, together with the loading potential of each receptor (n > 1) and Gaussian energies of approximately 8 kJ/mol, indicate the physical entrapment of 5-Fu molecules according to a vertical orientation. The materials mentioned verify long-term and continuous release characteristics. Following the modification processes, this behavior became faster as both CS@ZP/HP and CD@ZP/HP displayed complete release within 120 h at pH 1.2. The kinetic studies and diffusing exponent (>0.45) indicate that release characteristics are controlled by both diffusion and erosion processes. These carriers also markedly increase the cytotoxicity of 5-Fu against HCT-116 colorectal cancer cell lines: 5-Fu-ZP/HP (3.2% cell viability), 5-Fu-CS@ZP/HP (1.12% cell viability), and 5-Fu-CD@ZP/HP (0.63% cell viability).

9.
Eur J Clin Pharmacol ; 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39327261

RESUMEN

BACKGROUND: The dosing of voriconazole is challenging in pediatrics. One approach to improve the dosing is through the use of Bayesian concentration-guided dosing software. Our study assessed the predictive performance of a freely available online voriconazole dose calculator in pediatric patients "NextDose" ( https://www.nextdose.org/ ). METHODS: Per each dose calculator, we predicted voriconazole concentrations. We did both a priori and a posteriori Bayesian predictions. RESULTS: A total of 51 patients were included in this study. For a priori predictions, bias was + 26% while imprecision was 70%. For a posteriori predictions, bias and imprecision were 0.01% and 46%. DISCUSSION: In conclusion, the available online dose calculator was overpredicting the concentrations before voriconazole observations were available. However, with just one measured concentration, the predictions improved with minimal bias and an acceptable level of imprecision. There is a need for more prospective studies evaluating the use of voriconazole dosing calculators in the pediatric population to assess if they can improve the achievement of therapeutic target concentrations compared to standard of care.

10.
Br J Psychiatry ; : 1-7, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291442

RESUMEN

BACKGROUND: Clozapine is the most effective medication for treatment-resistant psychoses, but the balance of benefits and risks is understudied in real-world settings. AIMS: To examine the relative re-hospitalisation rates for mental health relapse and adverse events associated with clozapine and other antipsychotics in adult and child/youth cohorts. METHOD: Data were obtained from the Canadian Institute of Health Information for adults (n = 45 616) and children/youth (n = 1476) initially hospitalised for mental health conditions in British Columbia, Manitoba and Saskatchewan from 2008 to 2018. Patient demographics and hospitalisations were linked with antipsychotic prescriptions dispensed following the initial visit. Recurrent events survival analysis for relapse and adverse events were created and compared between clozapine and other antipsychotics. RESULTS: In adults, clozapine was associated with a 14% lower relapse rate versus other drugs (adjusted hazard ratio: 0.86, 95% CI: 0.83-0.90) over the 10-year follow-up. In the first 21 months, the relapse rate was higher for clozapine but then reversed. Over 1000 person-months, clozapine-treated adults could be expected to have 38 relapse hospitalisations compared with 45 for other drugs. In children/youth, clozapine had a 38% lower relapse rate compared with other antipsychotic medications (adjusted hazard ratio: 0.62, 95% CI: 0.49-0.78) over the follow-up period. This equates to 29 hospitalisations for clozapine and 48 for other drugs over 1000 person-months. In adults, clozapine had a higher risk for adverse events (hazard ratio: 1.34, 95% CI: 1.18-1.54) over the entire follow-up compared with other antipsychotics. This equates to 1.77 and 1.30 hospitalisations over 1000 person-months for clozapine and other drugs, respectively. CONCLUSIONS: Clozapine was associated with lower relapse overall, but this was accompanied by higher adverse events for adults. For children/youth, clozapine was associated with lower relapse all throughout and had no difference in adverse events compared with other antipsychotics.

11.
J Educ Health Promot ; 13: 236, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39297121

RESUMEN

Burnout is recognized as a negative contributor to well-being within healthcare. The purpose of this study was to evaluate whether participation in the Peace Education Program (PEP), a 10-week wellness course, promoted durable improvement of burnout and wellness in a large academic medical center. We deployed PEP virtually through a series of free, interactive, online wellness sessions focusing on 10 domains: peace, appreciation, inner strength, self-awareness, clarity, understanding, dignity, choice, hope, and contentment. Two weeks before and six months following the sessions, we distributed de-identified surveys based upon the validated Schwartz Outcome Scale-10 (SOS-10) with Likert scale scores 0-6 to assess participant wellness. The Mann-Whitney U test was used to analyze statistical differences between post- and pre-course data. Sixty-nine faculty, trainees, and staff registered to participate, 21 participants completed the pre-course survey and 10 completed the post-course survey. The pre-course mean + standard error (SE) SOS-10 score was 43.2 ± 0.8, which improved to 51.0 ± 0.7 post-course (P < 0.001). Overall, all 10 domains demonstrated improved mean scores over time, with the five domains of "inner strength" (P = 0.008), "understanding" (P = 0.030), "peace" (P = 0.048), "choice" (P = 0.026), and "hope" (P = 0.020) demonstrating statistically significant score improvements six months after course completion. Participants completing ≥7 sessions benefited more than their counterparts and achieved statistically significant improvement in SOS-10 wellness scores (8.77 points) six months after course completion. Our findings demonstrate improved wellness in participants following peace education course completion. This free, interactive, online course may be utilized at other medical centers to improve wellness.

12.
Clin Neurol Neurosurg ; 246: 108549, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39299007

RESUMEN

OBJECTIVE: Brain metastases (BM) constitute the most common intracranial tumor in adults. Prior literature indicates the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score is associated with increased risk of cancer, potentially attributable to shared risk factors. Understanding the role of ASCVD risk scores in BM may help optimize their care and inform clinical decision-making. Our aim was to explore associations between ASCVD risk score in BM patients and their overall survival, hospital charges, and non-routine discharge disposition. METHODS: Electronic medical records were reviewed to collect clinical data for BM patients undergoing surgery at a single institution (2017-2021). Regression analyses were performed accordingly and maximally selected rank statistics were employed to identify an optimal cutoff for ASCVD risk scores. The random survival forest (RSF) machine learning technique identified the most important variable associated with survival outcomes in BM patients. RESULTS: A total of 139 patients were included with average age 62.93±9.29 years, 48.2 % male, 25.2 % with high hospital charges, and 23.7 % experiencing non-routine discharge. Among these patients, 32.3 % had prior history of an ASCVD event, while 67.7 % did not. Overall, this cohort had an average 10-year ASCVD risk score of 12.51±12.98, indicating intermediate risk of ASCVD among all BM patients. On multivariate logistic regression, prior history of ASCVD was associated with higher odds of high hospital charges (OR=3.670, p=0.018), and higher ASCVD risk scores were associated with greater odds of non-routine discharge (OR=1.059, p=0.012). On the multivariate Cox regression model, higher ASCVD risk scores correlated with worse overall survival (HR=1.031, p=0.014). A threshold of 25.1 was identified for high-risk ASCVD scores. Patients with ASCVD scores >25.1 exhibited reduced overall survival in Kaplan-Meier analysis (p=0.015) and multivariate Cox regression (HR: 2.811, p=0.016). Notably, ASCVD risk scores were found to be the most important variable in predicting worse survival outcomes in BM patients compared to other established frailty indices. CONCLUSION: This study indicates higher ASCVD risk scores in BM patients are associated with worse overall survival. Integrating ASCVD assessment into clinical workflow may facilitate more informed risk-based decision-making.

13.
Cureus ; 16(9): e69749, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39308838

RESUMEN

The orthotopic ileal neobladder is becoming a popular technique of urinary diversion after radical cystectomy (RC) for localized muscle-invasive bladder cancer (MIBC), allowing patient continence, with a more desirable body image and good quality of life. Minimally invasive robot-assisted RC and neobladder have the potential to minimize physical and psychological trauma and are increasingly being adopted for patients with MIBC worldwide. Spontaneous perforation of orthotopic neobladder is uncommon;however, it represents serious complications. Solitary binge drinking can be dangerous in a patient with a neobladder because of reduced level of consciousness and overdistension of the neobladder. We report a case of spontaneous ileal neobladder perforations one year post-robotic RC secondary to blackouts from binge drinking. We also describe nonoperative active management and review the literature. A 66-year-old gentleman was brought by ambulance to our emergency department with a reduced level of consciousness, vomiting, and abdominal pain in the early hours of the morning. Collateral history revealed that he had drunk alcohol alone the night before at his home where he lives alone. Initial examination revealed tachycardia and hypotension. Immediate resuscitation using the sepsis six protocol included intravenous normal saline, blood culture, broad-spectrum antibiotic, lactate measurement, and insertion of a urethral catheter to monitor urine output. Following contrast-enhanced computed tomography (CECT) of the abdomen and pelvis, the patient was referred to a urologist. A diagnosis of spontaneous perforation of the neobladder was made. A nonoperative or 'conservative' management approach was adopted with careful active monitoring at the intensive care unit (ICU) involving a multidisciplinary team. Follow-up CT was performed to assess radiological recovery. The patient recovered successfully and was discharged home five weeks post-admission with an indwelling urethral catheter. The catheter was removed 10 weeks post-admission following a cystogram confirming the integrity of the neobladder. The patient has preserved neobladder function and continence and is doing well until the last follow-up at six months post-discharge. Patients with neobladder should be rigorously counseled about the importance of timed voiding, intermittent self-catheter, serious consequences of solitary binge drinking, and urinary retention.

14.
Clin Pract ; 14(5): 1716-1736, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39311287

RESUMEN

BACKGROUND AND OBJECTIVES: Accelerated orthodontics represents a significant shift in dental practice aimed at reducing treatment times while maintaining optimal patient outcomes. This bibliometric analysis evaluated the research landscape of accelerated orthodontics from 2012 to 2023, focusing on publication trends, citation patterns, influential journals, leading institutions, and key contributors. MATERIALS AND METHODS: A comprehensive search in Scopus identified 600 relevant articles, with the top 50 most-cited papers encompassing systematic reviews, randomized controlled trials, and experimental studies. Key techniques, such as corticotomy and piezocision, have been frequently highlighted for their effectiveness in expediting tooth movement. RESULTS: The analysis revealed fluctuating annual scientific outputs, with notable peaks driven by technological advancements and increased patient demand for quicker orthodontic solutions. However, the production of high-impact papers was hindered by delays in citation accumulation and disruptions caused by the COVID-19 pandemic. Keyword analysis identified critical themes, such as orthodontic tooth movement, malocclusion, and demographic factors, while a global collaboration map underscored extensive international research partnerships. Leading journals included the American Journal of Orthodontics and Dentofacial Orthopedics, and prominent institutions such as the University of California at Los Angeles played significant roles in advancing the field. CONCLUSIONS: This study provides a comprehensive overview of the current state of accelerated orthodontics, emphasizing the need for continued research, particularly RCTs, to further refine and validate accelerated orthodontic techniques and improve clinical outcomes.

15.
Pharm Dev Technol ; : 1-14, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39264666

RESUMEN

The low and erratic oral absorption of sulpiride (SUL) a dopaminergic receptor antagonist, and its P-glycoprotein efflux in the gastrointestinal tract restricted its oral route for central nervous system disorders. An intranasal formulation was formulated based on nanostructured lipid carrier to tackle these obstacles and deliver SUL directly to the brain. Sulipride-loaded nanostructured lipid carrier (SUL-NLC) was prepared using compritol®888 ATO and different types of liquid lipids and emulsifiers. SUL-NLCs were characterized for their particle size, charge, and encapsulation efficiency. Morphology and compatibility with other NLC excipients were also studied. Moreover, SUL in vitro release, nanodispersion stability, in vivo performance and SUL pharmacokinetics were investigated. Results delineates that SUL-NLC have a particle size ranging from 366.2 ± 62.1 to 640.4 ± 50.2 nm and encapsulation efficiency of 75.5 ± 1.5%. SUL showed a sustained release pattern over 24 h and maintained its physical stability for three months. Intranasal SUL-NLC showed a significantly (p < 0.01) higher SUL brain concentration than that found in plasma after oral administration of commercial SUL product with 4.47-fold increase in the relative bioavailability. SUL-NLCs as a nose to brain approach is a promising formulation for enhancing the SUL bioavailability and efficient management of neurological disorders.

16.
Alzheimers Dement ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39282876

RESUMEN

INTRODUCTION: Brain magnetic resonance imaging (MRI) and inflammatory biomarkers are crucial for investigating preclinical neurocognitive disorders. Current investigations focus on a few inflammatory markers. The study aims to investigate the associations between inflammatory biomarkers and MRI measures and to examine sex differences among the associations in the Framingham Heart Study. METHODS: Dementia and stroke-free participants underwent OLINK Proteomics profiling and MRI measurements within 5 years. Pairwise cross-sectional analysis assessed 68 biomarkers with 13 brain MRI volumes, adjusting for covariates and familial correlations. RESULTS: Elevated CDCP1, IL6, OPG, and 4E.BP1 were related to smaller total cerebral brain volume (TCBV), whereas higher HGF, IL8, and MMP10 were associated with smaller TCBV, total and frontal white matter volumes. Higher SCF and TWEAK were associated with larger TCBV. In sex-stratified analyses, associations were observed exclusively among males. DISCUSSION: We report several associations between inflammatory biomarkers and brain volumes, highlighting different associations within sex subgroups. HIGHLIGHTS: Higher CDCP1, IL6, OPG, and 4E.BP1 levels were associated with smaller TCBV. Higher levels of HGF, IL8 and MMP10 were associated with smaller TCBV, CWV and FWV. Higher levels of SCF and TWEAK, were associated with larger TCBV. Significance diminished in models adjusting for CVD risk factors. Associations were observed exclusively in males.

17.
Asian J Surg ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39271317

RESUMEN

BACK GROUND: A common pedicled facial technique in head and neck reconstruction is the TMF It can be utilised to replace missing tissues in a variety of conditions, including oral deformities of the hard and soft palate. AIM: Aim of the study was to document the utility and outcomes with the reconstruction of the palate using TM flaps following Maxillectomy For maxillary sinus malignancies. METHODOLOGY: The study included 24 patients who were operated on for cancer maxilla and eligible for maxillectomy and reconstruction of the Palate using temporalis flap. Follow-up was planned for at least 12 months postoperative. Postoperative physical and speech therapy are initiated to help improve speech and swallow outcomes and to prevent trismus. RESULTS: The current study included 24 cases with Maxillary sinus cancer with a mean age of 42.34 ± 4.67. The mean operative time was 5.4 ± 1.22 h with no reported intraoperative bleeding or injury of important structures. No cases of facial palsy or trismus were reported while partial flap loss was reported in one case where oronasal fistula was evident. The donor site complications were minimal where seroma occurred in two patients and alopecia, wound infection and dehiscence were reported in one case each. The donor site depression was evident in 25 % of cases. CONCLUSION: TMF is an excellent option for the reconstruction of many craniofacial defects, it is easy to be harvested with good blood supply with minimal postoperative complications.

18.
Prenat Diagn ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39272224

RESUMEN

OBJECTIVE: Congenital viral infection may result in fetal anemia and thrombocytopenia. While intrauterine blood transfusions (IUTs) are more commonly performed for Rh alloimmunization, reports using IUT for infection have varying success. Our primary objective was to characterize the outcomes of patients undergoing IUT for infectious etiologies at our center compared with Rh disease. STUDY DESIGN: This was a case series of patients undergoing IUT from 2012-2023. Infectious etiologies were identified by maternal serologies and confirmed by amniotic fluid polymerase chain reactions (PCR). Clinical outcomes were obtained from electronic medical records. RESULTS: During the study period, 70 patients underwent IUT, 34% (24/70) for Rh alloimmunization and 17% (12/70) for infection. Those with infectious etiologies were more likely to be diagnosed at earlier gestational ages (22 vs. 25 weeks, p = 0.04), with hydrops (75 vs. 33%, p = 0.03), and thrombocytopenia (27 ± 33 × 103 vs. 163 ± 112 × 103, p < 0.01). Perinatal death was significantly greater in cases of CMV (4/5, 80%) compared to parvovirus (1/7, 14%) or Rh alloimmunization (5/24, 21%) (p = 0.02). CONCLUSION: Anemias and thrombocytopenias related to fetal infection may be indications for IUT. Compared with Rh alloimmunization, IUT in fetal infections was performed significantly earlier, and hydrops were more common at the time of IUT. In the case of CMV, greater rates of IUFD (80%) were observed. Patients should be counseled on the various outcomes by indication.

19.
Water Res ; 267: 122441, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293341

RESUMEN

Effective disinfection is essential for maintaining water quality standards in distribution networks. Chlorination, as the most used technique, ensures safe water by maintaining sufficient chlorine residuals but also leads to the formation of disinfection byproducts (DBPs). These DBPs pose health risks, highlighting the need for chlorine injection control (CIC) by booster stations to balance safety and DBPs formation. Prior studies have followed various approaches to address this research problem. However, most of these studies overlook the changing flow conditions and their influence on the evolution of the chlorine and DBPs concentrations by integrating simplified transport-reaction models into CIC. In contrast, this paper proposes a novel CIC method that: (i) integrates multi-species dynamics, (ii) allows for a more accurate representation of the reaction dynamics of chlorine, other substances, and the resulting DBPs formation, and (iii) optimizes for the regulation of chlorine concentrations subject to EPA mandates thereby mitigating network-wide DBPs formation. The novelty of this study lies in its incorporation of time-dependent controllability analysis that captures the control coverage of each booster station. The effectiveness of the proposed CIC method is demonstrated through its application and validation via numerical case studies on different water networks with varying scales, initial conditions, and parameters.

20.
Curr Probl Cardiol ; : 102832, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293774

RESUMEN

BACKGROUND: Retrograde approach has notably improved success rates of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). However, longer procedural time, increase use of fluoroscopy and contrast dye have been reported in retrograde techniques in CTO PCI. We aimed to study in-hospital and long-term outcomes of retrograde approach versus antegrade approach in CTO PCI. METHODS: We searched PubMed, Scopus, WOS, and Cochrane Central until June, 2023 to include all relevant studies that compared retrograde approach versus antegrade approach in patients with CTO PCI. We synthesized the outcome data using a random-effects model, expressing the effect estimates as odds ratios (OR) or mean difference (MD) with corresponding 95% confidence intervals (CI). RESULTS: A total of 18 studies comprising 18,830 patients were included in the analysis. Regarding in-hospital outcomes, antegrade approach was associated with lower odds of MACE (OR= 0.34, 95% CI: 0.23 to 0.51), all-cause mortality (OR= 0.35, 95% CI: 0.19 to 0.64), MI (OR= 0.36, 95% CI: 0.25 to 0.53), urgent pericardiocentesis (OR= 0.27, 95% CI: 0.16 to 0.46), CIN (OR= 0.46, 95% CI: 0.33 to 0.65), procedural complications (OR= 0.52, 95% CI: 0.33 to 0.83), target vessel perforation (OR= 0.45, 95% CI: 0.32 to 0.64). while antegrade was associated with higher success rates (OR= 1.16, 95% CI: 1.1 to 1.22). CONCLUSION: Compared to antegrade technique, retrograde was associated with higher risk for in-hospital and long-term adverse events, and preferably should be performed in more complex CTO lesions.

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