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1.
Biotechnol J ; 19(9): e202400305, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39295543

RESUMEN

Cobalamin (VB12) is in enormous demand across the fields of medicine, food, and feed additives. However, the oxygen supply plays a critical role in VB12 biosynthesis by Ensifer adhaerens Casida A and has been identified as a bottleneck for economical substrate consumption. This study elucidates the relationship between oxygen limitation and VB12 accumulation with transcriptomic and metabolomic analyses. Under oxygen limitation, E. adhaerens enhances oxygen transport and storage by increasing expression of flavin hemoglobin (Hmp), which was up-regulated 6-fold at 24 h of oxygen restriction compared to the oxygen restriction of 4 h (p < 0.01). Because of the cofactor of Hmp is heme, the demand for heme increases, leading to the upregulation of genes in the heme biosynthesis pathway. Similarly, genes involved in biosynthesis of its precursor, 5-ALA, were upregulated as well. 5-ALA is also a direct precursor of VB12, further leading to the upregulation of genes in the VB12 biosynthesis pathway. This process initiates biosynthesis and accumulation of VB12. As VB12 and heme biosynthesis progresses, genes associated with the biosynthesis and transportation pathways of compounds related to their biosynthesis were likewise upregulated, including genes involved in S-adenosyl methionine (SAM) biosynthesis, and the transport of Fe2+ and Co2+. Additionally, amino acids and organic acids associated with biosynthesis were also extensively consumed, such as methionine, which is used for synthesizing SAM, decreased by 310% after 24 h of oxygen limitation compared to 20% dissolved oxygen (p < 0.05). At the same time, genes related to growth-associated metabolic pathways, such as pentose phosphate pathway (PPP), were significantly downregulated. Therefore, the potential mechanism by which E. adhaerens accumulates VB12 under oxygen-limited conditions by enhancing Hmp expression, which facilitates the porphyrin metabolic pathway and promotes VB12 biosynthesis. This research provides valuable insights for increasing VB12 production through metabolic engineering and process optimization.


Asunto(s)
Oxígeno , Vitamina B 12 , Oxígeno/metabolismo , Vitamina B 12/metabolismo , Hemo/metabolismo , Transcriptoma/genética
2.
Inflammopharmacology ; 32(5): 3311-3326, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39207636

RESUMEN

Rheumatoid arthritis (RA) is characterized by inflammatory joint pathology leading to the degradation of articular bone and cartilage, primarily triggered by synovial inflammation, resulting in joint discomfort. The metacarpophalangeal and proximal interphalangeal joints are predominantly affected. Treatment typically involves a combination of biological and synthetic disease-modifying antirheumatic drugs (DAMARDs) alongside steroid therapy. The application of nanomedicine has been instrumental in enhancing treatment efficacy by facilitating controlled release of pharmacologically active compounds, thus augmenting bioavailability and enabling targeted drug delivery. Gingerol, a constituent of ginger, possesses multifaceted properties. including anti-inflammatory, anti-oxidant, antidiabetic, and antipyretic effects. In this study, gingerol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), coated with chitosan, were administered orally to rats over a period of 21 days to address RA induced by complete Freund adjuvant (CFA). The rats were segregated into four experimental groups. Upon completion of the treatment regimen, blood samples were collected for the assessment of cyclooxygenase-2 (COX-2), RA factor, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Subsequent gene expression analysis was conducted to evaluate the levels of interleukin-4 (IL-4), interleukin-17a (IL-17a), IL-6, interferon-gamma (INF-γ), TNF-α, interleukin-1 beta (IL-1ß), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL). Statistical analyses utilizing one-way ANOVA followed by Tukey tests were applied to the data. The gene expression profiling revealed significant disparities in mRNA levels of IL-1ß, IL-6, IL-4, IL-17a, RANKL, INF-γ, and TNF-α between the CFA-induced arthritis group and the control group. Consequently, it was inferred that gingerol-loaded PLGA NPs coated with chitosan exhibited heightened therapeutic efficacy in addressing CFA-induced arthritis in rats.


Asunto(s)
Artritis Experimental , Catecoles , Alcoholes Grasos , Adyuvante de Freund , Nanopartículas , Osteoprotegerina , Ligando RANK , Transducción de Señal , Animales , Ratas , Ligando RANK/metabolismo , Nanopartículas/administración & dosificación , Artritis Experimental/tratamiento farmacológico , Catecoles/farmacología , Catecoles/administración & dosificación , Transducción de Señal/efectos de los fármacos , Osteoprotegerina/metabolismo , Masculino , Alcoholes Grasos/farmacología , Alcoholes Grasos/administración & dosificación , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificación , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Artritis Reumatoide/tratamiento farmacológico , Quitosano/farmacología , Ratas Wistar , Ratas Sprague-Dawley
3.
Acta Haematol ; : 1-12, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39191224

RESUMEN

INTRODUCTION/BACKGROUND: Reduced-intensity conditioning (RIC) and nonmyeloablative (NMA) regimens have enabled patients with cardiovascular disease (CVD) to undergo allogeneic stem cell transplantation (allo-HSCT). However, little is known about long-term outcomes, including cardiovascular (CV) complications. METHODS: We retrospectively studied 99 consecutive patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who underwent allo-HSCT between September 1, 2013, and November 30, 2020. Overall survival (OS), progression-free survival (PFS), nonrelapse mortality (NRM), cumulative incidence of relapse, and cumulative incidence of acute and chronic graft-versus-host disease (GvHD) were compared in patients with and without CV risk factors or disease. RESULTS: Preexisting CVD was present in 34 of 99 patients (34%). CVD patients more commonly had reduced-intensity conditioning (91% vs. 60%, p = 0.001) and unrelated donors (56% vs. 35%, p = 0.04). Early adverse cardiac events occurred more frequently in the CVD versus no-CVD group (38% vs. 14%), particularly arrhythmias (21% vs. 5%; p = 0.04). CVD patients tended to have poorer OS and PFS outcomes (HR = 1.98, [1.00, 3.92]; HR = 1.89, [0.96-3.72], respectively). OS rate at 1, 2, and 3 years for CVD versus no-CVD patients was 66% versus 72%, 55% versus 64%, and 46% versus 62%, respectively. Causes of death in the CVD and no-CVD groups were infections (53% vs. 28%), relapsed disease (32% vs. 52%), and CV events (10% vs. 3%). CONCLUSION: Based on these data, predictive models to identify patients with CVD with higher risk of post-allo-HSCT complications and mortality and strategies to mitigate these risks should be developed.

4.
Cureus ; 16(6): e62356, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39006567

RESUMEN

Introduction Hypoglycemia is a critical concern in neonatal care, particularly among preterm infants. This study aims to investigate the frequency of hypoglycemia within the first 24 hours of life in preterm neonates, considering factors such as gestational age (GA), birth weight, and gender. Materials and methods A cross-sectional study was conducted from February to August 2021. The sample comprised 186 preterm infants selected through consecutive sampling. Data collection involved demographic information, glucose level monitoring, and symptom assessment. Results Of the 186 preterm neonates, 31.7% (n=59) experienced hypoglycemia within the first 24 hours, with feeding refusal being the predominant symptom. There was a significant difference in hypoglycemia occurrence between infants born before and after 32 weeks of gestation (p<0.05). Males were slightly more affected than females, although not statistically significant. Infants weighing less than 2 kg showed a higher susceptibility to hypoglycemia. Conclusion The early detection and management of hypoglycemia are crucial in preterm neonatal care. Close monitoring, especially in the initial four hours, is essential to prevent complications. Larger studies are warranted to confirm these findings and improve understanding and management strategies for hypoglycemia in preterm neonates, particularly within the first 24 hours of life.

5.
Clin Linguist Phon ; : 1-19, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637977

RESUMEN

This study explores the perceptions of facilitators, barriers to communication and strategies in Malaysian school-aged children with non-syndromic cleft lip and palate (CL/P), parents, and teachers. Fourteen children with non-syndromic CL/P aged 7 to 12 years, their parents (n = 16), and their teachers (n = 10) were recruited via purposive sampling. Participants were selected based on resilience scores (RS-10; (Wagnild, 2015) distinguishing low (<34) from high resilience (35-40) (Wagnild, 2015). Individual in-depth interviews were conducted online and evaluated qualitatively. The analyses were conducted utilising the guidelines by Braun and Clarke (2006). Inductive thematic analysis was performed. Facilitators for communication identified by children, parents and teachers were the child's personal attributes, common interests, and helping others. Barriers that were identified were unfamiliar conversation partners, and insensitive comments or questions. Children used passive (e.g. ignored) and active (e.g. retorted, explained the condition) strategies to address social communication issues. Children with high resilience responded more actively than children with low resilience. Strategies that were described by the parents included accepting the child, empowering themselves, following the cleft management plan, and empowering the child. Teachers adopted general approaches such as giving encouragement, increasing confidence, and teaching empathy. The presence of face masks was perceived as both a facilitator and a barrier to communication. The study provides information on challenges encountered and coping mechanisms used by children with non-syndromic CL/P, their parents and their teachers. This knowledge may help the development of targeted interventions to support the communication of children with non-syndromic CL/P in school.

6.
World J Surg ; 48(5): 1159-1166, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38578243

RESUMEN

BACKGROUND: Axillary lymph node dissection (ALND) in breast cancer management, necessitates a nuanced understanding of complications that may impede treatment progression. This study scrutinize the impact of Haemoblock hemostatic solution, evaluation it's potential in reducing seroma complication by controlling lymph flow and obliterating axillary dead space. METHOD: A prospective, randomized, double-blinded controlled trial was conducted with 58 patients undergoing breast conserving surgery (BCS) and ALND, stratified into two groups: Group A (ALND + Haemoblock, n = 29) and Group B (ALND + placebo, n = 29). Postoperative drainage charts were monitored, with the primary endpoint being the time to drain removal, Additionally, patients were observed for surgical site infection (SSI). RESULTS: Group A exhibited a marginally higher mean total drain output (398 +/- 205 vs. 326 +/- 198) compared to Group B, this difference did not attain statistical significance (p = 0.176). Equally, the mean time to drain removal demonstrated no discernible distinction between the two groups (6 +/- 3.0 vs. 6 +/- 3.0, Group A vs. Group B, p = 0.526). During follow up, nine patients in Group A required seroma aspiration (mean aspiration 31 +/- 73) as compared to Group B, 6 patients required aspiration (mean aspiration 12 +/- 36), p = 0.222). No notable disparity in SSI rates between the groups was identified. CONCLUSION: In conclusion, the administration of Haemoblock did not manifest a discernible effect in mitigating seroma production, hastening drain removal, or influencing SSI rates following ALND. The study underscores the intricate and multifactorial nature of seroma formation, suggesting avenues for future research to explore combined interventions and protracted follow-up periods for a more comprehensive understanding.


Asunto(s)
Axila , Neoplasias de la Mama , Hemostáticos , Escisión del Ganglio Linfático , Mastectomía Segmentaria , Seroma , Humanos , Seroma/prevención & control , Seroma/etiología , Femenino , Escisión del Ganglio Linfático/efectos adversos , Escisión del Ganglio Linfático/métodos , Persona de Mediana Edad , Neoplasias de la Mama/cirugía , Estudios Prospectivos , Método Doble Ciego , Mastectomía Segmentaria/efectos adversos , Mastectomía Segmentaria/métodos , Hemostáticos/uso terapéutico , Anciano , Drenaje , Adulto , Resultado del Tratamiento , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología
7.
Leuk Res ; 138: 107456, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38442593

RESUMEN

Incidence of both acute myeloid leukemia (AML) and cardiovascular disease (CVD) increases with age. We evaluated whether pre-existing CVD impacts clinical outcomes in AML. We retrospectively evaluated 291 consecutive adult AML patients treated at our institution, 2014-2020. Pretreatment comorbidities were identified by chart review. Outcomes included complete remission (CR) and CR with incomplete count recovery (CRi) rates, disease-free survival (DFS), overall survival (OS) and incidence of cardiovascular adverse events. CVD was present in 34% of patients at AML diagnosis. CVD patients had worse performance status (p=0.03) and more commonly had secondary AML (p=0.03) and received hypomethylating (HMA) agent-based therapy (72% vs 38%, p< 0.001). CVD (0.45 vs 0.71, p<0.001) and diabetes mellitus (HR= 0.24, 95% CI: 0.08 - 0.8, p= 0.01) were associated with lower probability of achieving CR/CRi. Accounting for age, performance status (PS), complex karyotype, secondary disease and treatment, CVD patients had shorter OS (HR=1.5, 95% CI: 1.1-2.2, p=0.002), with 1- and 3-year OS 44% vs 67% and 25% vs 40%, respectively, but there was no difference in cumulative incidence of relapse between patients with vs without CVD. Thus, CVD is an independent risk factor for lower response rate and shorter survival in AML patients.


Asunto(s)
Enfermedades Cardiovasculares , Leucemia Mieloide Aguda , Adulto , Humanos , Estudios Retrospectivos , Enfermedades Cardiovasculares/epidemiología , Inducción de Remisión , Leucemia Mieloide Aguda/tratamiento farmacológico , Supervivencia sin Enfermedad
8.
J Bioeth Inq ; 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38407763

RESUMEN

Rapid developments in science and technology have resulted in novel discoveries, leading to new questions particularly related to human values and ethics. Every discovery and technology has positive and negative implications and affects human lives either directly or indirectly, involving all walks of life. Bioethical discourse in Malaysia must consider the multiracial and multireligious background of Malaysia and especially the Islamic view as the majority of Malaysians are Muslims and Islam is the religion of the federation. This article discusses several selected bioethical issues in Malaysia by studying the application of maslahah (the public good) and mafsadah (evil and harms) in Malaysian Islamic rulings (fatwas). This article uses the critical interpretation approach, as this is an ethical, interpretive, textual, and contextual analysis. In a situation when there is a conflict between maslahah and avoidance of mafsadah, it is preferred to attempt to address both needs. However, if maslahah and avoidance of mafsadah are mutually exclusive, the decision to choose must be made by weighing (tarjih) and choosing the one which is superior. The maslahah and mafsadah concepts play vital and significant roles in bioethical discourse to realize human essential interests, namely faith, life, lineage, intellect, and property, thus achieving maqasid al-shari'ah (the ultimate goal of sharia). This concept helps in guiding bioethical discussions, especially in determining the priority between achieving benefits and avoiding harms. The application of this concept will also assist Malaysian authorities in formulating appropriate rulings, especially bioethical issues related to Malaysian Muslims' lives.

9.
Intest Res ; 22(3): 351-356, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38311714

RESUMEN

BACKGROUND/AIMS: To describe the role of ustekinumab in inducing remission and endoscopic healing in anti-tumor necrosis factor α nonresponsive pediatric ulcerative colitis patients at a tertiary care inflammatory bowel disease center. METHODS: A retrospective chart review was performed on patients with ulcerative colitis receiving ustekinumab. Primary outcome was steroidfree clinical remission at follow-up. Secondary outcomes were biochemical remission and endoscopic healing. RESULTS: Ten children were analyzed; 7 (70%) had ulcerative colitis, and 3 (30%) had inflammatory bowel disease unspecified with colitis. Median follow-up period was 56 weeks. Nine patients (90%) achieved steroid-free clinical remission and biochemical remission. Seven patients had follow-up colonoscopies, out of which 6 (86%) achieved endoscopic remission, while 1 (14%) underwent colectomy. Out of the 3 patients without a follow-up colonoscopy, fecal calprotectin levels downtrended to < 150 mg/kg in 2 patients and < 400 mg/kg in 1 patient from baseline level of > 2,000 mg/kg. CONCLUSIONS: Ustekinumab appears efficacious in achieving not only clinical and biochemical remission but also has promising role in inducing endoscopic healing end point in patients who fail other biologics.

10.
Infect Genet Evol ; 118: 105559, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38266757

RESUMEN

BACKGROUND: In this study, we have identified multiple mutations in the IL-12R1 gene among Pakistani patients who have inherited them through consanguineous marriages. These patients have experienced severe Bacille-Calmette-Guérin (BCG) infection as well as recurrent tuberculosis. We will demonstrate the pivotal role of interleukin (IL)-12/interferon (IFN)-γ axis in the regulation of mycobacterial diseases. METHODOLOGY: First, we checked the patients' medical records, and then afterward, we assessed interferon-gamma (IFN-γ) production through ELISA. Following that, DNA was extracted to investigate IL-12/IFN- abnormalities. Whole exome sequencing was conducted through Sanger sequencing. Secretory cytokine levels were compared from healthy control of the same age groups and they were found to be considerably less in the disease cohort. To evaluate the probable functional impact of these alterations, an in silico study was performed. RESULTS: The study found that the patients' PBMCs produced considerably less IFN-γ than expected. Analysis using flow cytometry showed that activated T cells lacked surface expression of IL-12Rß1. Exon 7 of the IL-12Rß1 gene, which encodes a portion of the cytokine binding region (CBR), and exon 10, which encodes the fibronectin-type III (FNIII) domain, were found to have the mutations c.641 A > G; p.Q214R and c.1094 T > C; p.M365T, respectively. In silico analysis showed that these mutations likely to have a deleterious effect on protein function. CONCLUSION: Our findings indicate the significant contribution of the IL-12/IFN-γ is in combating infections due to mycobacterium. Among Pakistani patients born to consanguineous marriages, the identified mutations in the IL-12Rß-1 gene provide insights into the genetic basis of severe BCG infections and recurrent tuberculosis. The study highlights the potential utility of newborn screening in regions with mandatory BCG vaccination, enabling early detection and intervention for primary immunodeficiencies associated with mycobacterial infections. Moreover, the study suggests at the potential role of other related genes such as IL-23Rß1, TYK2, or JAK2 in IFN-γ production, warranting further investigation.


Asunto(s)
Vacuna BCG , Tuberculosis , Recién Nacido , Humanos , Consanguinidad , Secuenciación del Exoma , Incidencia , Receptores de Interleucina-12/genética , Tuberculosis/epidemiología , Tuberculosis/genética , Interleucina-12/genética , Interleucina-12/metabolismo , Citocinas/genética , Interferón gamma/metabolismo
11.
Intestinal Research ; : 351-356, 2024.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1043124

RESUMEN

Background/Aims@#To describe the role of ustekinumab in inducing remission and endoscopic healing in anti-tumor necrosis factor α nonresponsive pediatric ulcerative colitis patients at a tertiary care inflammatory bowel disease center. @*Methods@#A retrospective chart review was performed on patients with ulcerative colitis receiving ustekinumab. Primary outcome was steroidfree clinical remission at follow-up. Secondary outcomes were biochemical remission and endoscopic healing. @*Results@#Ten children were analyzed; 7 (70%) had ulcerative colitis, and 3 (30%) had inflammatory bowel disease unspecified with colitis. Median follow-up period was 56 weeks. Nine patients (90%) achieved steroid-free clinical remission and biochemical remission. Seven patients had follow-up colonoscopies, out of which 6 (86%) achieved endoscopic remission, while 1 (14%) underwent colectomy. Out of the 3 patients without a follow-up colonoscopy, fecal calprotectin levels downtrended to 2,000 mg/kg. @*Conclusions@#Ustekinumab appears efficacious in achieving not only clinical and biochemical remission but also has promising role in inducing endoscopic healing end point in patients who fail other biologics.

12.
J Fluoresc ; 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38038875

RESUMEN

Waste peels are considered an environmental burden and typically disposed in landfills. The aim of this study was to investigate the effects of various solvents on the luminescence properties of carbon quantum dots (CQDs). Watermelon peels were recycled and reuse as precursors for the synthesis of biomass CQDs via a green carbonization method. The colloidal stability, surface charge, and particle size were characterized using zeta potential and dynamic light scattering (DLS). DLS revealed that the size of the CQDs was approximately 5.80 ± 0.4 nm to 9.74 ± 0.8 nm. The high-resolution transmission electron microscopy (HRTEM) results demonstrated a correlation with the DLS results. The optical properties were characterized by photoluminescence (PL) and UV-Visible (UV-Vis) spectroscopy. PL measurements at different excitation wavelengths revealed that the CQDs emissions were influenced by the polarity of the solvents. Meanwhile, the Fourier transform infra-red (FTIR) results showed the presence of oxygen-containing groups on the surface of the CQDs. These results deepen our understanding of the solvent-dependent behavior and colloidal stability of the CQDs.

13.
Cureus ; 15(7): e41991, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37593294

RESUMEN

Drugs that act on the calcitonin gene-related peptide (CGRP) pathway herald the dawn of a new era in the management of migraine headaches. The blockade of CGRP alleviates neural inflammation and has been associated with reduced pain sensitization. Zavegepant is a third-generation drug and is the first intranasal CGRP antagonist to be developed. This systematic review aims to assess the safety, efficacy, pharmacokinetics, and tolerability of Zavegepant as an abortive treatment for migraine. Studies that assessed the safety, tolerability, and efficacy of Zavegepant for migraine were identified through a systematic literature review of PubMed, Clinicaltrials.gov, and Cochrane databases in April 2023. Our systematic review yielded a total of six studies that fit our inclusion criteria. Of these, data from only two randomized control trials (RCTs) was homogenous; hence, forest plots of results pooled from the included studies were not reported. The included studies showed that Zavegepant is an efficacious and well-tolerated abortive treatment modality for episodic migraine in adult patients. Zavegepant showed safety and efficacy in migraine treatment according to various parameters throughout the six included studies. These parameters include adverse events, pharmacokinetic properties, CGRP inhibition, effect on blood pressure/electrocardiogram, pain freedom, and freedom from most bothersome symptoms.

14.
BDJ Open ; 9(1): 35, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37524702

RESUMEN

OBJECTIVE: To examine nationwide the knowledge, attitudes, and practices of healthcare professionals on oral/dental care of pregnant women in Brunei Darussalam. MATERIALS AND METHODS: A descriptive cross-sectional study conducted using an online survey of eligible healthcare professionals in all Government Maternal and Child Health Care Clinics, Dental Clinics and Obstetrics and Gynecological Clinics in four hospitals covering the whole of Brunei Darussalam. Participants were given seven days to complete the survey. Sub-group analysis using Chi-square test for independence and one-way Analysis of Variance (ANOVA) was used to determine the significant association between domains of oral care practices and demographic factors. P values less than 0.05 was considered statistically significant. RESULTS: A total of 346 healthcare professionals participated in this online study. Most participants (94.3%) responded that they perceived oral health to be of high importance. However, less than two thirds of the participants (59.0%) included oral health questions during antenatal health assessments. Moreover, only 16.2% of participants frequently discussed the importance of oral care with their antenatal patients. CONCLUSIONS: In this survey, most healthcare professionals viewed oral health to be of high importance for prenatal/antenatal patients. However, not all put those views into practice with regard to oral care in pregnant women.

15.
R I Med J (2013) ; 106(6): 35-39, 2023 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-37368832

RESUMEN

BACKGROUND: In 2016, ESPGHAN/NASPGHAN issued revised guidelines for the management of Helicobacter pylori (H. pylori) infection in children and adolescents. Recommendations include performing antibiotic susceptibility testing to tailor therapy. The aim of our study was to evaluate the H. pylori treatment landscape in pediatric patients at our institution. METHODS: We performed a retrospective study of patients diagnosed with H. pylori infection at a single academic children's hospital from 2015 to 2021. The frequency of each treatment regimen and their respective eradication rates were calculated. We compared trends in antibiotic prescriptions and eradication rates before and after 2016. RESULTS: One hundred and ninety-six patients were included. Triple therapy with amoxicillin, clarithromycin, and a proton pump inhibiter (PPI) was the most often prescribed regimen (46.5%), followed by amoxicillin, metronidazole, and PPI (33%). Eradication rates were 70% for amoxicillin, clarithromycin, and PPI and 64% for amoxicillin, metronidazole, and PPI. CONCLUSION: Our results show eradication rates for both regimens were comparable but suboptimal, highlighting the need to incorporate resistance testing into broader practice.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Adolescente , Humanos , Niño , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/etiología , Claritromicina/uso terapéutico , Claritromicina/efectos adversos , Metronidazol/uso terapéutico , Estudios Retrospectivos , Hospitales Pediátricos , Quimioterapia Combinada , Antibacterianos/uso terapéutico , Amoxicilina/uso terapéutico , Amoxicilina/efectos adversos , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/efectos adversos , Resultado del Tratamiento
16.
Molecules ; 28(11)2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37298851

RESUMEN

The work here reflects synthesis, DFT studies, Hirshfeld charge analysis and crystal data exploration of pharmacologically important (R)-2-(2-(1,3-dioxoisoindolin-2-yl)propanamido)benzoic acid methyl ester (5) to understand its properties for further chemical transformations. The methyl anthranilate (2) was produced by the esterification of anthranilic acid in an acidic medium. The phthaloyl-protected alanine (4) was rendered by the fusion of alanine with phthalic anhydride at 150 °C, followed by coupling with (2) furnished isoindole (5). The characterization of products was performed using IR, UV-Vis, NMR and MS. Single-crystal XRD also verified the structure of (5) in which N-H⋯O bonding stabilizes the molecular configuration of (5), resulting in the formation of S(6) hydrogen-bonded loop. The molecules of isoindole (5) are connected in the form of dimers, and the π⋯π stacking interaction between aromatic rings further stabilizes the crystal packing. DFT studies suggest that HOMO is over the substituted aromatic ring, the LUMO is present mainly over the indole side, and nucleophilic and electrophilic corners point out the reactivity of the product (5). In vitro and in silico analysis of (5) shows its potential as an antibacterial agent targeting DNA gyrase and Dihydroorotase from E. coli and tyrosyl-tRNA synthetase and DNA gyrase from Staphylococcus aureus.


Asunto(s)
Girasa de ADN , Ésteres , Teoría Funcional de la Densidad , Escherichia coli , Alanina , Ácido Benzoico , Isoindoles
17.
J Pediatr Gastroenterol Nutr ; 77(2): 207-213, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37084343

RESUMEN

OBJECTIVES: Infliximab (IFX) is commonly used to treat children with inflammatory bowel disease (IBD). We previously reported that patients with extensive disease started on IFX at a dose of 10 mg/kg had greater treatment durability at year one. The aim of this follow-up study is to assess the long-term safety and durability of this dosing strategy in pediatric IBD. METHODS: We performed a retrospective single-center study of pediatric IBD patients started on IFX over a 10-year period. RESULTS: Two hundred ninety-one patients were included (mean age = 12.61, 38% female) with a follow-up range of 0.1-9.7 years from IFX induction. One hundred fifty-five (53%) were started at a dose of 10 mg/kg. Only 35 patients (12%) discontinued IFX. The median duration of treatment was 2.9 years. Patients with ulcerative colitis ( P ≤ 0.01) and patients with extensive disease ( P = 0.01) had lower durability, despite a higher starting dose of IFX ( P = 0.03). Adverse events (AEs) were observed to occur at a rate of 234 per 1000 patient-years. Patients with a higher serum IFX trough level (≥20 µg/mL) had a higher rate of AEs ( P = 0.01). Use of combination therapy had no impact on risk of AEs ( P = 0.78). CONCLUSIONS: We observed an excellent IFX treatment durability, with only 12% of patients discontinuing therapy over the observed timeframe. The overall rate of AEs was low, the majority being infusion reactions and dermatologic conditions. Higher IFX dose and serum trough level> 20 µg/mL were associated with higher risk of AEs, the majority being mild and not resulting in cessation of therapy.


Asunto(s)
Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Humanos , Niño , Femenino , Lactante , Preescolar , Masculino , Infliximab/efectos adversos , Estudios Retrospectivos , Estudios de Seguimiento , Fármacos Gastrointestinales/efectos adversos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Colitis Ulcerosa/tratamiento farmacológico , Resultado del Tratamiento
18.
Micromachines (Basel) ; 14(2)2023 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-36838094

RESUMEN

Nanofiber membranes are starting to be used as an electrolyte storage medium because of their high porosity, which causes ionic conductivity, producing high energy. The ability of nanofiber membranes to absorb electrolytes proves their stability when used for a long time. In this study, the loading of acetylene carbon black (ACB) on polyacrylonitrile (PAN) is made by the electrospun method, which in turn is applied as an electrolyte medium in DSSC. Materials characterization was carried out through FTIR to determine the functional groups formed and SEM to observe morphology and diameter distribution. Furthermore, for DSSC performance, efficiency and EIS tests were carried out. The optimum nanofiber membrane was shown by esPACB1, with the highest efficiency reaching 1.92% with a porosity of 73.43%, nanofiber diameter of 172.9 ± 2.2 nm, an absorbance of 1850, and an electron lifetime of 0.003 ms.

19.
Sci Rep ; 13(1): 1395, 2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36697427

RESUMEN

A series of derivatives (DOCD2-DOCD6) with D-π-A configuration was designed by substituting various efficient donor moieties via the structural tailoring of o-DOC6-2F. Quantum-chemical approaches were used to analyze the optoelectronic properties of the designed chromophores. Particularly, M06/6-311G(d,p) functional was employed to investigate the non-linear optical (NLO) response (linear polarizability ⟨α⟩, first (ßtot) and second ([Formula: see text]tot) order hyperpolarizabilities) of the designed derivatives. A variety of analyses such as frontier molecular orbital (FMO), absorption spectra, transition density matrix (TDMs), density of states (DOS), natural bond orbital (NBO) and global reactivity parameters (GRPs) were employed to explore the optoelectronic response of aforementioned chromophores. FMO investigation revealed that DOCD2 showed the least energy gap (1.657 eV) among all the compounds with an excellent transference of charge towards the acceptor from the donor. Further, DOS pictographs and TDMs heat maps also supported FMO results, corroborating the presence of charge separation states along with efficient charge transitions. NBO analysis showed that π-linker and donors possessed positive charges while acceptors retained negative charges confirming the D-π-A architecture of the studied compounds. The λmax values of designed chromophores (659.070-717.875 nm) were found to have broader spectra. The GRPs were also examined utilizing energy band gaps of EHOMO and ELUMO for the entitled compounds. Among all the derivatives, DOCD2 showed the highest values of ßtot (7.184 × 10-27 esu) and [Formula: see text]tot (1.676 × 10-31 esu), in coherence with the reduced band gap (1.657 eV), indicating future potentiality for NLO materials.

20.
Fish Shellfish Immunol ; 132: 108455, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36464078

RESUMEN

Tilapia is one of the most common fish species that is intensively produced all over the world. However, significant measures at improving aquaculture health must be taken since disease outbreaks are often encountered in the rapidly developing aquaculture industry. Therefore, the objective of the study was designed to evaluate the metabolite changes in tilapia' sera through 1H NMR metabolomics in identifying the potential biomarkers responsible for immunomodulatory effect by the indigenous species of Malaysian microalgae Isochrysis galbana (IG). The results showed that IG-incorporated diet mainly at 5.0% has improved the immune response of innate immunity as observed in serum bactericidal activity (SBA) and serum lysozyme activity (SLA). The orthogonal partial least squares (OPLS) analysis indicated 5 important metabolites significantly upregulated namely as ethanol, lipoprotein, lipid, α-glucose and unsaturated fatty acid (UFA) in the 5.0% IG-incorporated diet compared to control. In conclusion, this study had successfully determined IG in improving aquaculture health through its potential use as an immune modulator. This work also demonstrated the effective use of metabolomics approach in the development of alternative nutritious diet from microalgae species to boost fish health in fulfilling the aquaculture's long-term goals.


Asunto(s)
Cíclidos , Haptophyta , Tilapia , Animales , Espectroscopía de Protones por Resonancia Magnética , Dieta/veterinaria , Inmunidad Innata , Metabolómica/métodos , Alimentación Animal/análisis
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