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2.
J Clin Med ; 13(13)2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38999498

RESUMEN

Background and Aims: Endoscopic sleeve gastroplasty (ESG) is a minimally invasive bariatric procedure to induce weight loss through restrictive physiology. This study was designed to evaluate the fluoroscopic measurement of gastric dimensions after ESG as a predictor of Total Body Weight Loss (TBWL) over time. Methods: Post-ESG patients were enrolled prospectively between August 2013 and August 2019. An upper gastrointestinal (GI) fluoroscopy was obtained within 7 days after the procedure. Two blinded, independent radiologists reviewed fluoroscopic images and measured the gastric lumen transverse diameter in three separate areas of the fundus, body, and antrum. The primary outcome was achieving a TBWL of ten percent or more after ESG. Results: In total, 162 patients were included in the analysis (65% female) and had a mean body mass index (BMI) of 39 ± 6 at baseline. Patients had a mean maximum TBWL of 16.5 ± 8.3%. Respectively, 92%, 75%, and 50% of patients achieved a TBWL of 5%, 10%, or 15% or more. The mean post-procedural UGI gastric fundus/antrum transverse measurement ratio was 1.2 ± 0.6. A higher fundus-to-antrum ratio was significantly associated with a TBWL of 10% or more during follow-up in the multivariable model (OR 2.49, 95% CI 1.31-4.71; p-value 0.005). The prediction score based on the fundus-to-antrum ratio hd an area under the ROC curve of 0.79 (95% CI 0.75-0.83) for predicting a TBWL of 10% or more during follow-up. Conclusions: Measuring gastric the fundus/antrum ratio within one week of endoscopic sleeve gastroplasty (ESG) is a consistent and independent predictive measure of sustained TBWL during long-term follow-up.

3.
Obes Surg ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965187

RESUMEN

Obesity is a complex disease process, which often requires multifactorial, patient-tailored strategies for effective management. Treatment options include lifestyle optimization, pharmacotherapy, endobariatrics, and bariatric metabolic endoscopy. Obesity-based interventions can be challenging in patient populations with severe obesity, particularly post-gastric bypass. We report the case of a non-surgical patient with a failed remote open gastric bypass, who underwent an endoscopic small bowel diversion procedure, resulting in partial caloric diversion, via the creation of an EUS-guided jejunocolostomy (EUS-JC). The procedure is an extension of prior reported EUS-guided and magnet-based small bowel bypass procedures, in this case, for the purposes of weight loss (Kahaleh et al., 1; Jonica et al. Gastrointest Endosc. 97(5):927-933, 2; Machytka et al. Gastrointest Endosc. 86(5):904-912, 3;). The procedure was performed without peri-procedural complications, with effective weight loss during follow-up. Endoscopic bariatric interventions that target the small bowel, such as EUS-JC, offer promising tools for obesity management and should be studied further. Numerous factors including lifestyle, psychosocial, genetic, behavioral, and secondary disease processes contribute to obesity. Severe obesity (defined as a BMI > 50 kg/m2) is associated with increased morbidity and mortality with a significantly reduced response to treatment (Flegal et al. JAMA. 309(1):71-82, 4;). Weight regain can be noted in up to 50% of patients post-RYGB. In populations with severe obesity, there is an associated 5-year surgical failure rate of 18% (Magro et al. Obesity Surg. 18(6):648-51, 5;). These patients may not be surgical candidates for revision or can develop post-revision chronic protein-caloric malnutrition (Shin et al. Obes Surg. 29(3):811-818, 6;). Lifestyle, modification, pharmacotherapy, or endoscopic transoral reduction (TORe) can be effective generally; however, in patients with severe obesity, the total desired excess body weight loss may not likely be accomplished solely by these strategies. An endoscopic small bowel intervention that diverts a portion of caloric intake from small bowel absorption can potentially promote weight loss similar to a surgical lengthening of the Roux limb (Shah et al. Obes Surg. 33(1):293-302, 7; Hamed et al. Annal Surg. 274(2):271-280, 8;), in the sense that there is a reduction in the total small bowel surface area for absorption. Roux limb distalization can be effective for weight regain for post bypass patients. The EUS-JC technique aims to work similarly by reducing the total small bowel surface area utilized for absorption. Since this patient was deemed a non-surgical candidate, an EUS-guided jejunocolostomy was offered. Prior to the procedure, the patient established longitudinal care with our bariatric nutritionist and obesity medicine services. Extensive pre-bariatric labs were screened to rule out confounders for recurrent severe obesity. Intra-procedure, the patient received one dose of 500 mg intravenous levofloxacin. Post-procedure, loperamide was prescribed every 8 h as needed for post-procedure diarrhea. Within 2 weeks, the patient was no longer taking anti-diarrheals. The post-procedure diet consisted of a liquid diet for 2 days before advancement to a low-residue diet for 1 month, and then a regular diet.

4.
RSC Adv ; 14(28): 19752-19779, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38899036

RESUMEN

Due to the importance of the fluorinated heterocycles as main components of marketed drugs where 20% of the anticancer and antibiotic drugs contain fluorine atoms, this review describes the reported five-membered heterocycles and their benzo-fused systems having directly connected fluorine atom(s). The in vivo and in vitro anticancer and antimicrobial activities of these fluorinated heterocycles are well reported. Some fluorinated heterocycles were found to be lead structures for drug design developments where their activities were almost equal to or exceeded the potency of the reference drugs. In most cases, the fluorine-containing heterocycles showed promising safety index via their reduced cytotoxicity in non-cancerous cell lines. SAR study assigned that fluorinated heterocycles having various electron-donating or electron-withdrawing substituents significantly affected the anticancer and antimicrobial activities.

5.
Clin Transl Sci ; 17(6): e13853, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38847347

RESUMEN

The evidence of rivaroxaban's pharmacokinetics in obese compared with non-obese populations remains inconclusive. We aimed to compare the pharmacokinetic profile of rivaroxaban between obese and non-obese populations under fed state. Participants who met the study's eligibility criteria were assigned into one of two groups: obese (body mass index ≥35 kg/m2) or non-obese (body mass index 18.5-24.9 kg/m2). A single dose of rivaroxaban 20 mg was orally administered to each participant. Nine blood samples over 48 h, and multiple urine samples over 18 h were collected and analyzed for rivaroxaban concentration using ultra-performance liquid chromatography coupled with tandem mass detector. Pharmacokinetic parameters were determined using WinNonlin software. Thirty-six participants were recruited into the study. No significant changes were observed between obese and non-obese participants in peak plasma concentration, time to reach peak plasma concentration, area under the plasma concentration-time curve over 48 h or to infinity, elimination rate constant, half-life, apparent volume of distribution, apparent clearance, and fraction of drug excreted unchanged in urine over 18 h. Rivaroxaban's exposure was similar between the obese and non-obese subjects, and there were no significant differences in other pharmacokinetic parameters between the two groups. These results suggest that dose adjustment for rivaroxaban is probably unwarranted in the obese population.


Asunto(s)
Inhibidores del Factor Xa , Obesidad , Rivaroxabán , Humanos , Rivaroxabán/farmacocinética , Rivaroxabán/administración & dosificación , Rivaroxabán/sangre , Masculino , Femenino , Adulto , Inhibidores del Factor Xa/farmacocinética , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/sangre , Persona de Mediana Edad , Administración Oral , Índice de Masa Corporal , Área Bajo la Curva , Semivida , Adulto Joven
6.
Arch Pharm (Weinheim) ; : e2400225, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38822393

RESUMEN

The current review outlines all possible recent synthetic platforms to quinoxaline derivatives and the potent stimulated apoptosis mechanisms targeted by anticancer therapies. The currently reported results disclosed that quinoxaline derivatives had promising anticancer potencies against a wide array of cancer cell lines, better than the reference drugs, through target inhibition. This review summarizes some potent quinoxaline derivatives with their synthesis strategies and their potential activities against various molecular targets. Quinoxalines can be considered an important scaffold for apoptosis inducers in cancer cells through inhibiting some molecular targets, so they can be further developed as target-oriented chemotherapeutics.

7.
JAMA Surg ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38865138
8.
Artículo en Inglés | MEDLINE | ID: mdl-38923387

RESUMEN

INTRODUCTION: The intersection between perinatal mental health and the coronavirus disease 2019 (COVID-19) pandemic remains of significant public health importance. The current study examined the emotional and financial well-being and predictors of elevated depressive symptoms among pregnant women during the COVID-19 pandemic. METHODS: This online survey was conducted with 2118 women ≥18 years old who were pregnant at the time of the survey and living in the United States or Puerto Rico. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale, with scores ≥10 indicative of elevated depressive symptoms. The final logistic regression model included housing insecurity, financial distress, COVID-19 diagnosis, exposure to COVID-19, and demographic covariates. RESULTS: More than half the sample (53.8%) had elevated depressive symptoms. In logistic regression analyses, the odds of having elevated depressive symptoms were significantly higher for participants reporting housing insecurity (adjusted odds ratio [aOR], 1.56; 95% CI, 1.22-2.01), financial distress (aOR, 1.57; 95% CI, 1.17-2.12), COVID-19 diagnosis (aOR, 2.53; 95% CI, 1.53-4.17), and COVID-19 exposure (aOR, 1.41; 95% CI, 1.07-1.86), after adjusting for covariates. The association of elevated depressive symptoms with housing insecurity was especially strong among those who experienced COVID-19 (aOR, 6.04; 95% CI, 2.15-17.0). DISCUSSION: Our findings are consistent with previous literature revealing that diagnosis, exposure, concerns about family, and effects on financial stability were related to depressive symptoms during the pandemic. The relationships between financial and housing concerns with elevated depressive symptoms, independent of concerns about infection in family members, suggest that there may be direct and indirect effects of the pandemic on mental health.

9.
J Alzheimers Dis ; 99(3): 1047-1064, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38758999

RESUMEN

Background: Higher allostatic load (AL), a multi-system measure of physiological dysregulation considered a proxy for chronic stress exposure, is associated with poorer global cognition (GC) in older non-Hispanic white adults. However, evidence of these associations in middle-aged and older US-based Hispanic/Latino adults is limited. Objective: To examine associations of AL with level of cognition, performance in cognition 7 years later, and change in cognition over 7 years among middle-aged and older US-based Hispanic/Latino adults. Methods: We used data (n = 5,799, 45-74 years at baseline) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation of Neurocognitive Aging (SOL-INCA). The AL score comprised 16 biomarkers representing cardiometabolic, glucose, cardiopulmonary, parasympathetic, and inflammatory systems (higher scores = greater dysregulation). Cognitive outcomes included GC and individual tests of verbal learning and memory, world fluency (WF), Digit Symbol Substitution (DSS), and Trail Making (Parts A & B). Survey-linear regressions assessed associations of AL with performance in cognition at baseline, 7 years later, and via 7-year cognitive change scores adjusting for sociodemographic characteristics, lifestyle factors, and depressive symptoms. Results: Higher AL was associated with lower baseline performance in GC and WF; and lower 7-year follow-up performance in these same measures plus DSS and Trail Making Parts A & B. Higher AL was associated with more pronounced 7-year change (reduction) in GC and on WF and DSS tests. Conclusions: Findings extend previous evidence in predominantly older non-Hispanic white cohorts to show that AL is related to level of and change in GC (as well as WF and DSS) among middle-aged and older US-based Hispanic/Latino adults.


Asunto(s)
Alostasis , Cognición , Hispánicos o Latinos , Pruebas Neuropsicológicas , Humanos , Masculino , Alostasis/fisiología , Femenino , Persona de Mediana Edad , Hispánicos o Latinos/psicología , Anciano , Cognición/fisiología , Pruebas Neuropsicológicas/estadística & datos numéricos , Envejecimiento/fisiología , Envejecimiento/psicología , Disfunción Cognitiva , Estados Unidos/epidemiología , Biomarcadores/sangre , Envejecimiento Cognitivo/fisiología
10.
Animals (Basel) ; 14(10)2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38791702

RESUMEN

Heat stress is one of the stressors that negatively affect broiler chickens, leading to a reduction in production efficiency and profitability. This reduction affects the economy in general, especially in hot and semi-hot countries. Therefore, improving heat tolerance of broiler chicks is a key to sustained peak performance, especially under adverse environmental heat stress conditions. The present study investigated three early feed withdrawal regimes (FWD) as a potential mitigation for thermal stress exposure. A total of 240 unsexed one-day-old Cobb-500 chicks were randomly recruited to one of four experimental groups using a completely randomized design (10 birds × 6 replicates). The experimental groups included the control group with no feed withdrawal (control), while the other three groups were subjected to early feed withdrawal for either 24 h on the 5th day of age (FWD-24), 12 h on the 3rd and 5th day of age (FWD-12), or 8 h on the 3rd, 4th, and 5th day of age (FWD-8), respectively. Production performance was monitored throughout the experiment. Meanwhile, blood and liver samples were taken at the end of the experimental period to evaluate major physiological dynamic changes. Our findings demonstrated that under chronic heat stress conditions, FWD treatments significantly improved broilers' production performance and enhanced several physiological parameters compared with the control. Serum levels of thyroid hormones were elevated, whereas leptin hormone was decreased in FWD groups compared with the control. Moreover, serum total protein, globulin, and hemoglobin levels were higher, while total cholesterol and uric acid were lower in the FWD groups. Furthermore, FWD groups showed significantly higher antioxidant marker activity with a significantly lower lipid peroxidation level. Immunoglobulin levels, lysozyme, complement factor C3, and liver heat shock protein 70 (HSP70) concentration were also elevated in FWD compared with the control. Also, serum interleukin-1ß (IL-1ß) and interferon-gamma (IFN-γ) significantly increased with FWD. Based on our findings, early feed withdrawal can be applied as a promising non-invasive nutritional strategy for broilers reared under chronic heat stress conditions. Such a strategy promotes the alleviation of the deleterious effects of heat stress on broiler performance, immunity, and redox status, owing to the onset of physiological adaptation and the development of thermotolerance ability.

11.
JAMA Netw Open ; 7(3): e240900, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38436958

RESUMEN

Importance: Although recent guidelines recommend against performance of preoperative urine culture before nongenitourinary surgery, many clinicians still order preoperative urine cultures and prescribe antibiotics for treatment of asymptomatic bacteriuria in an effort to reduce infection risk. Objective: To assess the association between preoperative urine culture testing and postoperative urinary tract infection (UTI) or surgical site infection (SSI), independent of baseline patient characteristics or type of surgery. Design, Setting, and Participants: This cohort study analyzed surgical procedures performed from January 1, 2017, to December 31, 2019, at any of 112 US Department of Veterans Affairs (VA) medical centers. The cohort comprised VA enrollees who underwent major elective noncardiac, nonurological operations. Machine learning and inverse probability of treatment weighting (IPTW) were used to balance the characteristics between those who did and did not undergo a urine culture. Data analyses were performed between January 2023 and January 2024. Exposures: Performance of urine culture within 30 days prior to surgery. Main Outcomes and Measures: The 2 main outcomes were UTI and SSI occurring within 30 days after surgery. Weighted logistic regression was used to estimate odds ratios (ORs) for postoperative infection based on treatment status. Results: A total of 250 389 VA enrollees who underwent 288 858 surgical procedures were included, with 88.9% (256 753) of surgical procedures received by males and 48.9% (141 340) received by patients 65 years or older. Baseline characteristics were well balanced among treatment groups after applying IPTW weights. Preoperative urine culture was performed for 10.5% of surgical procedures (30 384 of 288 858). The IPTW analysis found that preoperative urine culture was not associated with SSI (adjusted OR [AOR], 0.99; 95% CI, 0.90-1.10) or postoperative UTI (AOR, 1.18; 95% CI, 0.98-1.40). In analyses limited to orthopedic surgery and neurosurgery as a proxy for prosthetic implants, the adjusted risks for UTI and SSI were also not associated with preoperative urine culture performance. Conclusions and Relevance: This cohort study found no association between performance of a preoperative urine culture and lower risk of postoperative UTI or SSI. The results support the deimplementation of urine cultures and associated antibiotic treatment prior to surgery, even when using prosthetic implants.


Asunto(s)
Procedimientos Ortopédicos , Infección de la Herida Quirúrgica , Estados Unidos/epidemiología , Masculino , Humanos , Puntaje de Propensión , Estudios de Cohortes , Infección de la Herida Quirúrgica/diagnóstico , Infección de la Herida Quirúrgica/epidemiología , Urinálisis , Antibacterianos/uso terapéutico
12.
J Contemp Dent Pract ; 25(2): 180-185, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38514417

RESUMEN

AIM: To evaluate the intensity of postendodontic pain (PEP) using final irrigation with side-vented needle (SV), EndoActivator (EA), and Ultra X (UX) in single-visit endodontics (SVE) with F-One rotary files. MATERIALS AND METHODS: A total 150 patients indicated for endodontic treatment were selected. Single-visit endodontics treatment was performed under local anesthesia. For the final irrigation protocol, they were divided into three groups: group I (SV), group II (EA), and group III (UX). The severity of PEP was assessed using visual analogue scale (VAS) score after 6, 12, 24, and 48 hours. Analgesics taken by patients, for pain, were also recorded. Finally, the data were tabulated and statistically analyzed using SPSS 20.0 software at a level of significance being 0.05. RESULTS: Postendodontic pain was less in group III (UX) and group II (EA) compared with group I (SV) at 6 and 12 hours, which is statistically significant (p < 0.05). There was no statistically significant difference found after 24 hours and 48 hours. CONCLUSION: The intensity of PEP was minimum in patients treated with EndoActivator and ultrasonic along with single rotary file systems. The incidence of analgesic intake was similar in all three groups. How to cite this article: Kathiria NV, Attur K, Bagda KM, et al. Postendodontic Pain Using Single File System with Different Irrigation Protocols in Single-visit Root Canal Treatment: A Randomized Control Trial. J Contemp Dent Pract 2024;25(2):180-185.


Asunto(s)
Cavidad Pulpar , Preparación del Conducto Radicular , Humanos , Dolor Postoperatorio , Ensayos Clínicos Controlados Aleatorios como Asunto , Preparación del Conducto Radicular/métodos , Tratamiento del Conducto Radicular/métodos , Ultrasonido , Método Doble Ciego
13.
Sci Adv ; 10(13): eadm9859, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38536921

RESUMEN

Loss-of-function mutations in KEAP1 frequently occur in lung cancer and are associated with poor prognosis and resistance to standard of care treatment, highlighting the need for the development of targeted therapies. We previously showed that KEAP1 mutant tumors consume glutamine to support the metabolic rewiring associated with NRF2-dependent antioxidant production. Here, using preclinical patient-derived xenograft models and antigenic orthotopic lung cancer models, we show that the glutamine antagonist prodrug DRP-104 impairs the growth of KEAP1 mutant tumors. We find that DRP-104 suppresses KEAP1 mutant tumors by inhibiting glutamine-dependent nucleotide synthesis and promoting antitumor T cell responses. Using multimodal single-cell sequencing and ex vivo functional assays, we demonstrate that DRP-104 reverses T cell exhaustion, decreases Tregs, and enhances the function of CD4 and CD8 T cells, culminating in an improved response to anti-PD1 therapy. Our preclinical findings provide compelling evidence that DRP-104, currently in clinical trials, offers a promising therapeutic approach for treating patients with KEAP1 mutant lung cancer.


Asunto(s)
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Glutamina/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Inhibidores Enzimáticos/uso terapéutico , Mutación
15.
Braz J Biol ; 83: e276530, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38422267

RESUMEN

A significant public health issue worldwide is metabolic syndrome, a cluster of metabolic illnesses that comprises insulin resistance, obesity, dyslipidemia, hyperglycemia, and hypertension. The creation of natural treatments and preventions for metabolic syndrome is crucial. Chitosan, along with its nanoformulations, is an oligomer of chitin, the second-most prevalent polymer in nature, which is created via deacetylation. Due to its plentiful biological actions in recent years, chitosan and its nanoformulations have drawn much interest. Recently, the chitosan nanoparticle-based delivery of CRISPR-Cas9 has been applied in treating metabolic syndromes. The benefits of chitosan and its nanoformulations on insulin resistance, obesity, diabetes mellitus, dyslipidemia, hyperglycemia, and hypertension will be outlined in the present review, highlighting potential mechanisms for the avoidance and medication of the metabolic syndromes by chitosan and its nanoformulations.


Asunto(s)
Quitosano , Dislipidemias , Hiperglucemia , Hipertensión , Resistencia a la Insulina , Síndrome Metabólico , Humanos , Síndrome Metabólico/tratamiento farmacológico , Quitosano/uso terapéutico , Obesidad
16.
JAMA Surg ; 159(6): 706-707, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38170498

RESUMEN

This Guide to Statistics and Methods describes common methods for building evidence of validity for a program within health professional education and provides a framework for program evaluation.


Asunto(s)
Evaluación de Programas y Proyectos de Salud , Humanos
17.
J Immunol ; 212(4): 632-644, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38180236

RESUMEN

Distinct subsets of T lymphocytes express CX3CR1 under inflammatory conditions, but little is known about CX3CR1+CD4+ T cells during type 2 inflammation in helminth infections. In this study, we used a fate-mapping mouse model to characterize CX3CR1+CD4+ T cells during both acute Nippostrongylus brasiliensis and chronic Schistosoma mansoni murine models of helminth infections, revealing CX3CR1+CD4+ T cells to be an activated tissue-homing subset with varying capacity for cytokine production. Tracking these cells over time revealed that maintenance of CX3CR1 itself along with a TH2 phenotype conferred a survival advantage in the inflamed tissue. Single-cell RNA sequencing analysis of fate-mapped CX3CR1+CD4+ T cells from both the peripheral tissue and the spleen revealed a considerable level of diversity and identified a distinct population of BCL6+TCF-1+PD1+CD4+ T cells in the spleen during helminth infections. Conditional deletion of BCL6 in CX3CR1+ cells resulted in fewer CX3CR1+CD4+ T cells during infection, indicating a role in sustaining CD4+ T cell responses to helminth infections. Overall, our studies revealed the behavior and heterogeneity of CX3CR1+CD4+ T cells during type 2 inflammation in helminth infections and identified BCL6 to be important in their maintenance.


Asunto(s)
Linfocitos T CD4-Positivos , Helmintiasis , Schistosoma mansoni , Animales , Ratones , Linfocitos T CD4-Positivos/metabolismo , Helmintiasis/inmunología , Inflamación/metabolismo , Schistosoma mansoni/fisiología
18.
J Neuromuscul Dis ; 11(2): 425-442, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38250783

RESUMEN

Background: Long-term, real-world effectiveness and safety data of disease-modifying treatments for spinal muscular atrophy (SMA) are important for assessing outcomes and providing information for a larger number and broader range of SMA patients than included in clinical trials. Objective: We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting. Methods: RESTORE is a prospective, multicenter, multinational, observational registry that captures data from a variety of sources. Results: Recruitment started in September 2018. As of May 23, 2022, data were available for 168 patients treated with onasemnogene abeparvovec monotherapy. Median (IQR) age at initial SMA diagnosis was 1 (0-6) month and at onasemnogene abeparvovec infusion was 3 (1-10) months. Eighty patients (47.6%) had two and 70 (41.7%) had three copies of SMN2, and 98 (58.3%) were identified by newborn screening. Infants identified by newborn screening had a lower age at final assessment (mean age 11.5 months) and greater mean final (SD) CHOP INTEND score (57.0 [10.0] points) compared with clinically diagnosed patients (23.1 months; 52.1 [8.0] points). All patients maintained/achieved motor milestones. 48.5% (n = 81/167) experienced at least one treatment-emergent adverse event (AE), and 31/167 patients (18.6%) experienced at least one serious AE, of which 8/31 were considered treatment-related. Conclusion: These real-world outcomes support findings from the interventional trial program and demonstrate effectiveness of onasemnogene abeparvovec over a large patient population, which was consistent with initial clinical data and published 5-year follow-up data. Observed AEs were consistent with the established safety profile of onasemnogene abeparvovec.


Asunto(s)
Productos Biológicos , Atrofia Muscular Espinal , Proteínas Recombinantes de Fusión , Atrofias Musculares Espinales de la Infancia , Lactante , Recién Nacido , Humanos , Atrofias Musculares Espinales de la Infancia/tratamiento farmacológico , Estudios Prospectivos , Terapia Genética , Atrofia Muscular Espinal/tratamiento farmacológico , Sistema de Registros
19.
Eur Rev Med Pharmacol Sci ; 28(1): 39-48, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38235896

RESUMEN

OBJECTIVE: The aim of the study was to assess the disinfection efficacy, bond integrity, and nano hardness of caries-affected dentin (CAD) surface bonded to resin cement when disinfected with chlorhexidine (CHX), Methylene blue activated by Photodynamic therapy (MB-PDT), chitosan, silver diamine fluoride (SDF), chitosan activated by PDT, and SDF-diode laser against S. mutans. MATERIALS AND METHODS: A total of 60 human mandibular molars were extracted non-traumatically and gathered using ICDAS criteria. The dentin surface was prepared, leaving CAD to receive a disinfection procedure. After inoculation with S. mutans, the CAD samples were divided into six groups and disinfected with various disinfectants (n = 10) CHX, MB-PDT, chitosan, chitosan-PDT, SDF, and SDF+ diode laser. Survival rates of S. mutans were analyzed following the restoration of samples with resin cement via the etch and rinse method to assess SBS. Also, nano hardness was analyzed. Statistical analysis was performed by using the ANOVA and the Tukey multiple test (p<0.05). The Kruskal-Wallis test was used to evaluate the change in survival rate. RESULTS: Related to the survival rates, the SDF+ diode laser displayed the highest reduction in S. mutans levels and chitosan presented the lowest level of disinfection. The intergroup comparison revealed that CHX and chitosan-PDT displayed comparable outcomes of S. mutans survival rate to that of SDF+ diode laser (p>0.05). Likewise, MB-PDT and SDF displayed a comparable survival rate of S. mutans to Chitosan disinfection (p>0.05). Considering SBS and nano hardness, the highest SBS and NH were exhibited by the SDF+ diode laser, and the lowest SBS and NH values were exhibited by MB-PDT. The intragroup comparison revealed that CAD specimens disinfected with Chitosan-PDT showed comparable SBS and NH values to the SDF+ diode laser (p>0.05). CHX, chitosan, and SDF exhibited bond values and NH comparable to MB-PDT (p<0.05). CONCLUSIONS: Synergistic use of Silver diamine fluoride with diode laser and chitosan activated by PDT can be used as an alternative to CHX for controlling S. mutans growth, promoting enhanced bond efficacy and nano hardness for bonding resin cement to the caries-affected dentin.


Asunto(s)
Quitosano , Fotoquimioterapia , Compuestos de Amonio Cuaternario , Compuestos de Plata , Humanos , Azul de Metileno , Dentina , Desinfección , Adhesivos , Cementos de Resina , Susceptibilidad a Caries Dentarias , Clorhexidina/farmacología , Clorhexidina/uso terapéutico , Ensayo de Materiales , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fluoruros Tópicos
20.
Heliyon ; 10(1): e23586, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38173479

RESUMEN

Energy consumption and emissions of a vehicle are highly influenced by road contexts and driving behavior. Especially, driving on horizontal curves often necessitates a driver to brake and accelerate, which causes additional fuel consumption and emissions. This paper proposes a novel optimal ecological (eco) driving scheme (EDS) using nonlinear model predictive control (MPC) considering various road contexts, i.e., curvatures and surface conditions. Firstly, a nonlinear optimization problem is formulated considering a suitable prediction horizon and an objective function based on factors affecting fuel consumption, emissions, and driving safety. Secondly, the EDS dynamically computes the optimal velocity trajectory for the host vehicle considering its dynamics model, the state of the preceding vehicle, and information of road contexts that reduces fuel consumption and carbon emissions. Finally, we analyze the effect of different penetration rates of the EDS on overall traffic performance. The effectiveness of the proposed scheme is demonstrated using microscopic traffic simulations under dense and mixed traffic environment, and it is found that the proposed EDS substantially reduces the fuel consumption and carbon emissions of the host vehicle compared to the traditional (human-based) driving system (TDS), while ensuring driving safety. The proposed scheme can be employed as an advanced driver assistance system (ADAS) for semi-autonomous vehicles.

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