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1.
J Indian Soc Pedod Prev Dent ; 42(3): 217-225, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39250206

RESUMEN

BACKGROUND: The main goal of the pediatric dentist is to address and reduce children's fear and anxiety during the dental treatment, especially when conventional behavior-guiding strategies fail. In such cases, the use of pharmacological agents becomes an essential factor to consider. OBJECTIVE: The objective of the study was to compare the efficacy, safety, and acceptability of intranasal ketamine (INK) with the combination of intranasal midazolam and dexmedetomidine (INMzD) in pediatric dental patients for the procedural sedation. PATIENTS AND METHODS: Forty-seven children aged 3-9 years who required dental procedures such as extractions, pulpectomy, and restorations were randomly distributed into two groups using the envelope drawing method. Group INK received 7 mg/kg INK, whereas Group INMzD received a combination of midazolam spray (0.3 mg/kg) and atomized dexmedetomidine (3 µg/kg). RESULTS: INK showed faster onset, faster recovery, and shorter discharge time than INMzD. Both groups had acceptable physiological parameters and no postoperative complications. INK was more accepted by the patients than INMzD. CONCLUSIONS: In terms of efficacy, safety, and acceptability, INK outperformed the combination of INMzD for the procedural sedation.


Asunto(s)
Administración Intranasal , Sedación Consciente , Estudios Cruzados , Dexmedetomidina , Hipnóticos y Sedantes , Ketamina , Midazolam , Humanos , Dexmedetomidina/administración & dosificación , Midazolam/administración & dosificación , Niño , Preescolar , Ketamina/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Masculino , Femenino , Sedación Consciente/métodos , Anestesia Dental/métodos , Atención Dental para Niños/métodos , Ansiedad al Tratamiento Odontológico/prevención & control , Extracción Dental
2.
Asian J Endosc Surg ; 17(4): e13382, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39223711

RESUMEN

Since the last decade, iatrogenic injuries of ureter are increasingly common. We describe a case of 36-year-old young female, who underwent emergency cesarean section, presented to us after 3 weeks, with clear vaginal discharge. After evaluated with clinical examination and radiological investigations, she was found to have left uretero-uterine fistula and was successfully treated with robotic-assisted left uretero-uterine fistula repair by Lich-Gregoir technique.


Asunto(s)
Cesárea , Procedimientos Quirúrgicos Robotizados , Enfermedades Ureterales , Fístula Urinaria , Enfermedades Uterinas , Humanos , Femenino , Adulto , Cesárea/efectos adversos , Enfermedades Ureterales/etiología , Enfermedades Ureterales/cirugía , Fístula Urinaria/etiología , Fístula Urinaria/cirugía , Embarazo , Enfermedades Uterinas/cirugía , Enfermedades Uterinas/etiología , Fístula/etiología , Fístula/cirugía
3.
JAMA Cardiol ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259546

RESUMEN

Importance: South Asian adults in the US experience excess cardiovascular disease (CVD) compared with other racial and ethnic groups. The effectiveness and reach of guideline-recommended lifestyle interventions have not been evaluated in this population. Objective: To evaluate whether a culturally adapted, group lifestyle intervention will improve CVD risk factors more effectively than written health education materials among US South Asian adults. Design, Setting, and Participants: This single-blind randomized clinical trial was conducted from March 6, 2018, to February 11, 2023 at community sites in the Chicago, Illinois, metropolitan area. South Asian adults aged 18 to 65 years who were overweight or obese, had no history of CVD events, and had at least 1 additional CVD risk factor (hypertension, dyslipidemia, prediabetes, or diabetes) were eligible for inclusion. Intervention: A 16-week, culturally adapted, group-based lifestyle intervention led by community health coaches. Lifestyle modification counseling was delivered in English, Gujarati, Hindi, and Urdu. Participants tracked their diet and physical activity (PA) and received 4 optional group maintenance sessions between months 5 and 11 of follow-up. The intervention was delivered in person prior to the onset of the COVID-19 pandemic and via videoconference starting in March 2020. The control group received written health education materials, delivered monthly. Main Outcomes and Measures: Primary outcomes were the between-group differences in CVD risk factor changes from baseline to 12 months, including weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), glycated hemoglobin (HbA1c), and total cholesterol, estimated using multivariate mixed-effects regression models. Secondary outcomes were self-reported diet quality, PA, and self-efficacy, estimated using univariate mixed-effects regression models. Results: Among 549 randomized participants, 318 (57.9%) were women, and mean (SD) participant age was 49.2 (9.5) years. Mean differences in CVD risk factor changes from baseline to 12 months in the intervention vs control group were calculated for weight (mean difference, -0.07 kg; 95% CI, -0.55 to 0.42), SBP (mean difference, 0.47 mm Hg; 95% CI, -1.85 to 2.79), DBP (mean difference, 0.44 mm Hg; 95% CI, -1.06 to 1.95), cholesterol (mean difference, -2.47 mg/dL; 95% CI, -8.51 to 3.57), and HbA1c (mean difference, -0.07%; 95% CI -0.20% to 0.07%). Intervention participation was associated with greater improvements in dietary quality, PA, and self-efficacy than control. Conclusions and Relevance: In the SAHELI randomized clinical trial, a culturally adapted, group lifestyle intervention was not more effective than written health education materials for CVD risk factor reduction among US South Asian adults, but the intervention was associated with small improvements in self-reported health behaviors. Effective CVD prevention interventions for this elevated-risk population require further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT03336255.

4.
Bioorg Chem ; 153: 107809, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39270528

RESUMEN

Dopamine receptors are therapeutic targets for the treatment of various neurological and psychiatric disorders, including Parkinson's and Alzheimer's. Previously, PF-06649751 (tavapadon), PF-2562 and PW0464 have been discovered as potent and selective G protein-biased D1/D5 receptor agonists with optimal pharmacokinetic properties. However, no selective D5R agonist has been reported yet. In this context, we designed and synthesized forty non-catecholamines-based pyrimidine derivatives and identified four pyrimidine derivatives as selective D5R partial agonists. Using cAMP-based GloSensor assay in transiently transfected HEK293T cells with human D1 or D5 receptors, we discovered that compound 5c (4-(4-bromophenyl)-6-(2,4,5-trimethoxyphenyl)pyrimidin-2-amine) exhibited modest D5R agonist activity. This leads us to explore various modifications of this scaffold to improve the D5 agonist potency and efficacy. Using molecular docking, and rational design followed by their evaluation at D1 and D5 receptors for agonist activity, we identified three new derivatives, 5j, 5h, and 5e. The most potent compound of this series 5j (4-(4-iodophenyl)-6-(2,4,5-trimethoxyphenyl)pyrimidin-2-amine), exhibited EC50 of 269.7 ± 6.6 nM. Mice microsomal stability studies revealed that 5j is quite stable (>70 % at 1 hr). Furthermore, pharmacokinetic analysis of 5j (20 mg/kg, p.o) in C57BL/6j mice showed that 5j is readily absorbed via oral route of dosing and also enters into the brain (plasma Tmax: 1 h, Cmax: 51.10 ± 13.51 ng/ml; Brain Tmax: 0.5 h, Cmax: 22.54 ± 4.08 ng/ml). We further determined the in-vivo effect of 5j on cognition in scopolamine-induced amnesia in C57BL/6j mice. We observed that 5j (10 mg/kg, p.o) alleviated scopolamine-induced impairment in short-term memory and social recognition, which were blocked by D1/D5 antagonist SCH23390 (0.1 mg/kg, i.p.). Furthermore, 5j did not exhibit any cytotoxicity (up to 10 µM) or in vivo acute toxicity up to 200 mg/kg (p.o). These results strongly suggest that 5j could be further developed for treating neurological disorders wherein the D5 receptors play pivotal roles.

5.
Appl Environ Microbiol ; : e0101224, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39258917

RESUMEN

Bioconversion of abundant lactose-replete whey permeate to value-added chemicals holds promise for valorization of this expanding food processing waste. Efficient conversion of whey permeate-borne lactose requires adroit microbial engineering to direct carbon to the desired chemical. An engineered strain of Clostridium beijerinckii NCIMB 8052 (C. beijerinckii_mgsA+mgR) that produces 87% more butanol on lactose than the control strain was assessed for global transcriptomic changes. The results revealed broadly contrasting gene expression patterns in C. beijerinckii_mgsA+mgR relative to the control strain. These were characterized by widespread decreases in the abundance of mRNAs of Fe-S proteins in C. beijerinckii_mgsA+mgR, coupled with increased differential expression of lactose uptake and catabolic genes, iron uptake genes, two-component signal transduction and motility genes, and genes involved in the biosynthesis of vitamins B5 and B12, aromatic amino acids (particularly tryptophan), arginine, and pyrimidines. Conversely, the mRNA patterns suggest that the L-aspartate-dependent de novo biosynthesis of NAD as well as biosynthesis of lysine and asparagine and metabolism of glycine and threonine were likely down-regulated. Furthermore, genes involved in cysteine and methionine biosynthesis and metabolism, including cysteine desulfurase-a central player in Fe-S cluster biosynthesis-equally showed reductions in mRNA abundance. Genes involved in biosynthesis of capsular polysaccharides and stress response also showed reduced mRNA abundance in C. beijerinckii_mgsA+mgR. The results suggest that remodeling of cellular and metabolic networks in C. beijerinckii_mgsA+mgR to counter anticipated effects of methylglyoxal production from heterologous expression of methylglyoxal synthase led to enhanced growth and butanol production in C. beijerinckii_mgsA+mgR. IMPORTANCE: Biological production of commodity chemicals from abundant waste streams such as whey permeate represents an opportunity for decarbonizing chemical production. Whey permeate remains a vastly underutilized feedstock for bioproduction purposes. Thus, enhanced understanding of the cellular and metabolic repertoires of lactose-mediated production of chemicals such as butanol promises to identify new targets that can be fine tuned in recombinant and native microbial strains to engender stronger coupling of whey permeate-borne lactose to value-added chemicals. Our results highlight new genetic targets for future engineering of C. beijerinckii for improved butanol production on lactose and ultimately in whey permeate.

6.
Biomed Pharmacother ; 179: 117379, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39255739

RESUMEN

SCOPE: Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition of unknown etiology, although recent evidence suggests that it is caused by an excessive immune response to mucosal antigens. We determined the anti-inflammatory properties of novel compound DJ-X-013 in vitro in lipopolysaccharide (LPS)-induced macrophages and in an in vivo dextran sodium sulfate (DSS)-induced model of colitis. METHODS AND RESULTS: To evaluate the anti-inflammatory properties of DJ-X-013, we used LPS-activated RAW 264.7 macrophages in vitro and a DSS-induced experimental model of colitis in vivo. We examine cellular morphology, and tissue architecture by histology, flow cytometry, RT-qPCR, multiplex, and immunoblot analysis to perform cellular and molecular studies. DJ-X-013 treatment altered cell morphology and expression of inflammatory cytokines in LPS-activated macrophages as compared to cells treated with LPS alone. DJ-X-013 also impeded the migration of RAW 264.7 macrophages by modulating cytoskeletal organization and suppressed the expression of NF-κB and inflammatory markers as compared to LPS alone. DJ-X-013 treatment improved body weight, and colon length and attenuated inflammation in the colon of DSS-induced colitis. Intriguingly, DSS-challenged mice treated with DJ-X-013 induced the numbers of myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), and natural killer T cells (NKT) in the colon lamina propria (LP) relative to DSS. DJ-X-013 also reduced the influx of neutrophils, TNF-α producing macrophages, restricted the number of Th17 cells, and suppressed inflammatory cytokines and NF-κB in the LP relative to DSS. CONCLUSION: DJ-X-013 is proposed to be a therapeutic strategy for ameliorating inflammation and experimental colitis.

7.
Pathol Res Pract ; 262: 155559, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39216321

RESUMEN

INTRODUCTION: Glioma is a brain tumour occurring in all age groups but common in adults. Despite advances in the understanding of tumours, we cannot improve the survival of the patients and do not have an appropriate biomarker for progression and prognosis prediction. The base excision repair mechanism maintains the integrity of the genome, preventing tumour formation. However, continuous chemical damage to the cells results in mutations that escape the repair mechanism and support tumour growth. The tumour microenvironment in cancer is crucial in determining the tumour growth, development, and response to treatments. The present study explored the significance of Base Excision Repair genes (BER) in modulating the tumour microenvironment. METHODS: We used the publically available data sets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to explore the role of the base excision repair gene in the modulating tumour microenvironment. The data was analysed for the expression of base excision repair genes, their correlation with the immune markers, their prognostic potential, and enrichment analysis to understand the pathways they modulate in low-grade glioma (LGG) progression. RESULTS: The analysis showed BER genes contribute an integral role in the overall and disease-free survival of LGG. Genes like MUTYH, PNKP, UNG and XRCC1 showed a correlation with the immune infiltration levels and a significant correlation with various immune markers associated with different immune cells, including tumour-associated macrophages. MUTYH, UNG and XRCC1 correlated with IDH1 mutation status, and functional enrichment analysis showed that these genes are enriched in several pathways like Wnt, PD-1 and Integrin signalling. CONCLUSION: Our findings suggest that the BER genes MUTYH, PNKP, UNG and XRCC1 can potentially be prognostic biomarkers and highly correlate with the immune cells of the tumour microenvironment.


Asunto(s)
Neoplasias Encefálicas , Reparación del ADN , Glioma , Microambiente Tumoral , Humanos , Glioma/genética , Glioma/patología , Glioma/inmunología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/inmunología , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Reparación del ADN/genética , Biomarcadores de Tumor/genética , Pronóstico , Regulación Neoplásica de la Expresión Génica/genética , Reparación por Escisión
9.
JMIR Form Res ; 8: e54999, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39094107

RESUMEN

BACKGROUND: Preventative self-care can reduce dental disease that disproportionately burdens vulnerable populations. Personalized digital oral self-care behavioral interventions offer a promising solution. However, the success of these digital interventions depends on toothbrushing data collection e-platforms attuned to the needs and preferences of vulnerable communities. OBJECTIVE: The aim of this study is to assess the usability and feasibility of the Remote Oral Behaviors Assessment System (ROBAS), which has been adapted to address the unique requirements of socioeconomically disadvantaged minority individuals. METHODS: A cohort of 53 community-clinic participants, including 31 (58%) Latino and 22 (42%) Black individuals with no prior experience using electric toothbrushes, were recruited to use ROBAS, with planned assessments at baseline, 2 months, and 4 months. Beyond evaluating ROBAS's technical performance, extensive feedback was gathered to gauge users' experiences, viewpoints, and overall contentment. The System Usability Scale (SUS) served as a primary metric for assessing user satisfaction and acceptability. RESULTS: ROBAS exhibited largely reliable and consistent data-gathering capabilities. SUS scores (mean 75.6, SD 14.5) reflected participant contentment within a range of values for other commonly used digital devices and technologies. Among participants who answered questions about willingness to pay for ROBAS, 97% (30/31) indicated that they were willing to pay for ROBAS either as a one-time payment or as a subscription-based service. Additionally, 87.5% of participants expressed that they would endorse it to acquaintances. Most participants expressed no reservations about privacy; among those who expressed privacy concerns (n=20, 50%), the concerns included exposure of information (n=18, 45%), monitoring of brushing habits (n=12, 30%), and collection of information (n=14, 35%), although these concerns did not significantly correlate with specific participant traits. In qualitative terms, users valued ROBAS's ability to monitor brushing habits but called for refinements, especially in Wi-Fi and application connectivity. Recommendations for system improvements encompassed enhanced app functionality, individualized coaching, more comprehensive brushing data, and the addition of flossing activity tracking. CONCLUSIONS: The research highlights ROBAS's promise as a digital platform for unobtrusively tracking daily oral self-care activities in marginalized communities. The system proved to be both feasible, as evidenced by its stable and accurate data capture of brushing behaviors, and user-friendly, as reflected by strong SUS scores and positive user feedback. Influential factors for its uptake included ease of learning and operation, and the feedback provided.

10.
Exp Biol Med (Maywood) ; 249: 10123, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39119118

RESUMEN

Antiretroviral drugs have made significant progress in treating HIV-1 and improving the quality of HIV-1-infected individuals. However, due to their limited permeability into the brain HIV-1 replication persists in brain reservoirs such as perivascular macrophages and microglia, which cause HIV-1-associated neurocognitive disorders. Therefore, it is highly desirable to find a novel therapy that can cross the blood-brain barrier (BBB) and target HIV-1 pathogenesis in brain reservoirs. A recently developed 2-amino-3-methylpentanoic acid [2-morpholin-4-yl-ethyl]-amide (LM11A-31), which is a p75 neutrotrophin receptor (p75NTR) modulator, can cross the BBB. In this study, we examined whether LM11A-31 treatment can suppress HIV-1 replication, oxidative stress, cytotoxicity, and inflammatory response in macrophages. Our results showed that LM11A-31 (100 nM) alone and/or in combination with positive control darunavir (5.5 µM) significantly suppresses viral replication and reduces cytotoxicity. Moreover, the HIV-1 suppression by LM11A-31 was comparable to the HIV-1 suppression by darunavir. Although p75NTR was upregulated in HIV-1-infected macrophages compared to uninfected macrophages, LM11A-31 did not significantly reduce the p75NTR expression in macrophages. Furthermore, our study illustrated that LM11A-31 alone and/or in combination with darunavir significantly suppress pro-inflammatory cytokines including IL-1ß, IL-8, IL-18, and TNF-α and chemokines MCP-1 in HIV-induced macrophages. The suppression of these cytokines and chemokines by LM11A-31 was comparable to darunavir. In contrast, LM11A-31 did not significantly alter oxidative stress, expression of antioxidant enzymes, or autophagy marker proteins in U1 macrophages. The results suggest that LM11A-31, which can cross the BBB, has therapeutic potential in suppressing HIV-1 and inflammatory response in brain reservoirs, especially in macrophages.


Asunto(s)
VIH-1 , Macrófagos , Morfolinas , Replicación Viral , VIH-1/efectos de los fármacos , Humanos , Replicación Viral/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/virología , Morfolinas/farmacología , Estrés Oxidativo/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Darunavir/farmacología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Receptores de Factor de Crecimiento Nervioso/metabolismo , Citocinas/metabolismo , Isoleucina/análogos & derivados , Proteínas del Tejido Nervioso
11.
Dalton Trans ; 53(32): 13638-13661, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39087793

RESUMEN

Multinuclear (di/tri) copper(II) complexes bridged through hydroxyl groups are very interesting coordination complexes owing to their potential applications in various fields. In this work, three novel dinuclear (µ-hydroxo)-bridged copper(II) complexes in the crystal form, namely, [Cu2(3,5-DIFLB)2(H2tea)2](H2O) (1), [Cu2(4-ClB)2(H2tea)2](H2O) (2), and [Cu2(4-ETHB)2(H2tea)2](H2O)2 (3) (where DIFLB = difluorobenzoate, CLB = chlorobenzoate, ETHB = ethoxybenzoate, and H3tea = triethanolamine), were isolated at room temperature using methanol and water in a 4 : 1 v/v ratio as a solvent. Furthermore, all three complexes (1-3) were characterised using spectroscopic (UV-vis, DRS, and FT-IR), electrochemical (CV) and single-crystal X-ray diffraction techniques. Structural insights gained by packing analysis revealed the role of steric constraints of substituents and various non-covalent interactions in lattice stabilization, which were indeed supported by theoretical and molecular electrostatic potential illustrations. Hirshfeld surface analysis provided quantitative verification about various non-covalent interactions (interatomic contacts) involved in the packing of molecules. Interestingly, as a potential application, complexes 1-3 all exhibited remarkable visible light-mediated photo-Fenton degradation of approximately 98% for 50 ppm concentration of organic dyes (fuchsin basic (FB) and methyl orange (MO)) in 90 minutes with the optimized conditions of 1 mg mL-1 of dye solution. In all the cases, dye degradation by these materials was ascribed to the symbiotic relations among the molecular structures of complexes 1-3, which were endowed with various electron-withdrawing and electron-releasing substituents and ionic strength, with respect to the structure, shape and interacting patterns of dye molecules. The adsorption mechanism indicates that various weak interactions between the donor and acceptor groups of complexes and dyes, such as electrostatic, hydrogen bonding, and direct coordination to metal sites, play a crucial role, which is confirmed by molecular dynamics (MD) simulations. Theoretical studies by DFT-based descriptors, molecular electrostatic potentials, and band gaps provided deep insights into various electronic and reactivity parameters. For subsequent processes of dye degradation, complexes 1-3 were stable and recoverable. The successful integration of experimental and theoretical approaches sheds light on copper-based dinuclear stable coordination complexes, showcasing a significant step towards the development of novel heterogeneous photo-Fenton catalysts.

12.
Int J Biol Macromol ; 279(Pt 2): 135162, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39214209

RESUMEN

Industrial and academic chemical pollutants such as Eriochrome Black-T (EBT) and murexide dyes are widely used in academic institution as well as industries, when eluted into rivers, delineate the ill effect on human and aquatic life. Herein, green and ecofriendly synthesis of silver doped-Zinc oxide nanoparticles (Ag/ZnO NPs) and chitosan coated Ag/ZnO nanoparticles (CS/Ag/ZnO NPs) using Bergera koenigii extract to solve environmental issues have been reported for the first time. Spherical and agglomerated particles with crystalline flakes like morphology of Ag/ZnO NPs and CS/Ag/ZnO NPs respectively have been ascertained by Scanning electron morphology (SEM) analyses and XRD. XRD analysis revealed the average crystallite size of 42.16 nm and 48.45 nm for Ag/ZnO NPs with 5 % and 10 % Ag concentration respectively, lesser than crystallite size of 47.394 nm and 52.38 nm for CS-5 % Ag/ZnO NC and CS-10 % Ag/ZnO NC respectively. All the synthesized NPs and NC demonstrated remarkable antibacterial potential against both gram +ve and gram -ve bacteria. Additionally, all the materials showed very high time-dependent photocatalytic degradation activity (>98 %) of EBT and murexide in 12 min. Remarkably, all active nano-catalysts exhibit high durability, and displayed recyclability for >8 cycles. In nutshell, chitosan coated nano-catalyst showed drastic improvement in photocatalytic and antibacterial activities.

13.
Clin Infect Dis ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39194339

RESUMEN

BACKGROUND: Treatment of drug-resistant tuberculosis with bedaquiline-pretomanid-linezolid regimen has demonstrated good treatment efficacy. Given linezolid's toxicity profile, prudence suggests reconsidering its dose and duration. We determined the effectiveness and safety of structured dose reduction of linezolid with bedaquiline and pretomanid in adults with pre-extensively drug-resistant (pre-XDR) or treatment-intolerant/nonresponsive multidrug-resistant (MDRTI/NR) pulmonary tuberculosis. METHOD: Adults with pre-XDR or MDRTI/NR pulmonary tuberculosis were enrolled in a multicenter, parallel-group, randomized clinical trial in India. Patients were randomized to 26 weeks of bedaquiline, pretomanid, and daily linezolid, at 600 mg for 26 weeks (arm 1); 600 mg for 9 weeks followed by 300 mg for 17 weeks (arm 2); or 600 mg for 13 weeks followed by 300 mg for 13 weeks (arm 3). Study end points included sustained cure, bacteriological failure, toxicity, and death. RESULTS: Of 403 patients enrolled, 255 (63%) were <30 years old, 273 (68%) had prior tuberculosis episodes, and 238 (59%) were malnourished. At the end of treatment, after excluding those with negative baseline cultures, cure was seen in 120 (93%), 117 (94%), and 115 (93%) in arms 1, 2, and 3 respectively. Myelosuppression seen in 85 patients each in arms 1 and 2 and 77 patients in arm 3, not significantly different. Peripheral neuropathy was noticed in 66 patients (30, 17, and 19 in arms 1, 2, and 3) at 10-26 weeks (P = .02). The linezolid dose was reduced because of toxicity in 13, 2, and 4 patients in arms 1, 2, and 3, respectively. CONCLUSIONS: In adults with pre-XDR or MDRTI/NR pulmonary tuberculosis, structured linezolid dose reduction to 300 mg/d is as effective as the standard 600-mg dose but with fewer cases of peripheral neuropathy when given with bedaquiline and pretomanid. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry of India (CTRI/2021/03/032189).

14.
Int J Biol Macromol ; 278(Pt 4): 135022, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39182895

RESUMEN

Antimicrobial resistance (AMR) poses a significant global health threat, rendering standard antibiotics ineffective against multi-drug resistant bacteria. To tackle this urgent issue, innovative approaches are essential. Liposomes, small spherical vesicles made of a phospholipid bilayer, present a promising solution. These vesicles can encapsulate various medicines and are both biocompatible and biodegradable. Their ability to be modified for targeted tissue or cell uptake makes them an ideal drug delivery system. By delivering antibiotics directly to infection sites, liposomes minimize side effects and reduce the development of resistance. However, challenges such as poor stability and rapid drug leakage limit their biological application. Chitosan, a biocompatible polymer, enhances liposome interaction with specific tissues or cells, enabling selective drug release at infection sites. Incorporating chitosan into liposome formulations alters and diversifies their surface characteristics through electrostatic interactions, resulting in improved stability and pH-sensitive drug release. These interactions are crucial for enhancing drug retention and targeted delivery, especially in varying pH environments like tumor sites or infection areas, thereby improving therapeutic outcomes and reducing systemic side effects. This review discusses recent advancements, challenges, and the need for further research to optimize liposome formulations and enhance targeted drug delivery for effective AMR treatment. Chitosan-modified liposomes offer a promising strategy to overcome AMR and improve antimicrobial therapies.


Asunto(s)
Antibacterianos , Quitosano , Portadores de Fármacos , Farmacorresistencia Bacteriana Múltiple , Liposomas , Quitosano/química , Liposomas/química , Portadores de Fármacos/química , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Humanos , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Sistemas de Liberación de Medicamentos , Animales , Liberación de Fármacos , Bacterias/efectos de los fármacos
15.
Front Plant Sci ; 15: 1401135, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39184577

RESUMEN

Cuticular waxes coating leaf surfaces can help plants tolerate drought events by reducing non-stomatal water loss. Despite their role in drought tolerance, little is known about how cuticular wax composition has changed during breeding in Canadian bread wheat (Triticum aestivum L.) varieties. To fill in this gap, flag leaves of the Canadian Heritage Bread Wheat Panel, which include 30 varieties released between 1842 and 2018, were surveyed to determine if and how cuticular wax composition in wheat has changed at two breeding ecozones over this period. Following this, a subset of varieties was subjected to drought conditions to compare their responses. As expected, modern varieties outperformed old varieties with a significantly larger head length and reaching maturity earlier. Yet, when challenged with drought, old varieties were able to significantly increase the accumulation of ß-diketones to a higher extent than modern varieties. Furthermore, RNAseq was performed on the flag leaf of four modern varieties to identify potential markers that could be used for selection of higher accumulation of cuticular waxes. This analysis revealed that the W1 locus is a good candidate for selecting higher accumulation of ß-diketones. These findings indicate that the variation in cuticular waxes upon drought could be further incorporated in breeding of future bread wheat varieties.

16.
J Orthop Case Rep ; 14(8): 212-221, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39157488

RESUMEN

Introduction: Bone cementation has various effects on hemodynamics including potentially fatal bone cement implantation syndrome (BCIS). Most of the studies on BCIS are from developed countries. We have studied the effect of bone cement on hemodynamics in hip arthroplasty in the eastern Indian population and compared it with the available literature. Materials and Methods: This prospective study was done by a team of orthopedic surgeons and anesthesiologists in a tertiary center in eastern India between March 2020 and December 2022. Result: Seventy-two patients (Male 38: and Female 34) of age between 25 and 100 years fulfilling the inclusion criteria were included. In 43 patients (43/72, 59.72%) systolic and diastolic blood pressure fell in the range of 10 mmHg, in 22 patients (22/72, 30.56%) fall in blood pressure was in the range of 10-20 mmHg, and more than 20 mmHg fall in blood pressure were seen in seven patients (7/72, 9.72%). SPO2 decreased from 97-100% to 94-96% in 28 patients and 90-93% in six patients, which began to rise after 5 min of cementing and returned to normal after 10 min. Arrhythmias were seen in 16 patients with multiple comorbidity. Two patients had a cardiac arrest and one patient died after 6 h in the intensive care unit. Conclusion: Pre-operative evaluation, perioperative monitoring of hemodynamic parameters during cementing especially in high-risk patients with multiple comorbidities, and taking essential precautions during cemented arthroplasty are the key to preventing complications like BCIS.

17.
Cureus ; 16(7): e65148, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39176307

RESUMEN

BACKGROUND: Chronic total occlusion (CTO) lesions are the most challenging subset of coronary lesions. For lesions with a failed antegrade approach, the initial retrograde, followed by a combined retrograde and antegrade approach, remains the mainstay of therapy. OBJECTIVE: The study evaluated a technique of initial retrograde followed by an antegrade approach to treat lesions with a failed antegrade approach. METHODS: We have adopted this technique to treat 31 CTO lesions with a failed antegrade approach, where a floppy wire was advanced antegrade through the tract created by a retrograde balloon advanced over the retrograde wire (antegrade wire tracking of the retrograde tract (ATRT)), which was advanced into the aorta retrogradely. RESULT: In 31 patients with failed antegrade approaches, the ATRT technique was tried, which was successful in 25 patients (the success rate was 80.6%). There was a failure to cross the microchannel in four patients, although angiographically, it looked promising. In two patients, it was impossible to advance the microcatheter or the smallest profile balloon retrogradely until the entire length of the CTO body. So, a reverse controlled antegrade and retrograde subintimal tracking (CART) was performed on these two patients excluded from the study. CONCLUSION: ATRT is a useful technique for CTO percutaneous coronary intervention (PCI) for patients with failed antegrade approaches with acceptable success rates. The procedure is safe in terms of procedural complications.

18.
Cureus ; 16(8): e67032, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39157000

RESUMEN

Introduction Salinity intrusion is the most common global concern along coastlines, but it can happen inland also. The lack of freshwater is the primary issue affecting the coastal areas. Many health problems are prevalent among the inhabitants due to their frequent use of salted water. The health of women living along the coastline is getting progressively compromised due to salinity intrusion. Objectives The study aims to determine menstrual health practices and other health problems faced by women in the coastal region of Bangladesh. Methods The study was conducted using a survey research design from May 2023 to October 2023 on rural women aged 18 to 45 years, who lived in the Bangladeshi village of Koyra Upazila in the Khulna district. The sample size of the study was 101. Open- and closed-ended questions from a planned interview schedule were used to gather primary data. Additional information from appropriate sources, e.g., newspapers, publications, and books, was utilized to enhance the comprehensiveness of statistical analysis and support rationality. A p-value of 0.05 was considered significant. Statistical analysis was performed using STATA version 15 (StataCorp LLC, College Station, TX). Results Menstrual hygiene practices showed a higher prevalence of using fabric rags and reusing them after rinsing them in salt water (72.3%) than sanitary pads (25.7%). It was observed that the risk of diarrhea among tubewell water and rainwater users was significantly lowered by 0.25 times (95% CI = 0.06, 0.99; p = 0.049) and 0.06 times (95% CI = 0.01, 0.43; p = 0.005), respectively, compared to pond water users. Conclusion Salinity has a significant impact on the livelihoods and health of coastal women. The village women are unaware of the health risks of excessive saline water use. Establishing an adequate supply of freshwater reservoirs for the entire community throughout the year is an alternative for women to use as a source of water for hygiene necessities.

19.
Med Sci Educ ; 34(4): 865-871, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39099861

RESUMEN

Purpose: This study explores the current knowledge and overall awareness of the faculty at an Apex institute about the use and difficulties of scenario-based multiple-choice questions (SB-MCQs), short-answer questions (SB-SAQs), and modified essay questions (SB-MEQs) in the assessment of the undergraduate and postgraduate students. Objectives: To assess faculty perception of awareness and use of SB-MCQs, SB-SAQs, and SB-MEQs and to understand the challenges encountered while designing scenario-based questions (SBQs) and the ways to overcome them. Study Procedure: The tool used for data collection was a Google form questionnaire designed with a total of 16 questions-12 Likert-scale format items and four open-ended questions. The quantitative data collected as a response to close-ended questions was analyzed by descriptive statistics and percentage values. For qualitative data, thematic analysis was done for open-ended questions. Conclusion: The study showed that the faculty has the motivation and agreeability to switch over from traditional questions to scenario-based questions but constant training in the form of regular faculty development programs and workshops is required for its effective implementation. On the administrative level, challenges like lack of sufficient faculty and proper inter-departmental integration for designing scenarios must be addressed. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-024-02052-6.

20.
Cureus ; 16(7): e63775, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39100036

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) and periodontitis share common risk factors such as obesity, insulin resistance (IR), and dyslipidemia, which contribute to systemic inflammation. It has been suggested that a bidirectional relationship exists between NAFLD and periodontitis, indicating that one condition may exacerbate the other. NAFLD is characterized by excessive fat deposition in the liver and is associated with low-grade chronic inflammation. There are several risk factors for the development of NAFLD, including gender, geriatric community, race, ethnicity, poor sleep quality and sleep deprivation, physical activity, nutritional status, dysbiosis gut microbiota, increased oxidative stress, overweight, obesity, higher body mass index (BMI), IR, type 2 diabetes mellitus (T2DM), metabolic syndrome (MetS), dyslipidemia (hypercholesterolemia), and sarcopenia (decreased skeletal muscle mass). This systemic inflammation can contribute to the progression of periodontitis by impairing immune responses and exacerbating the inflammatory processes in the periodontal tissues. Furthermore, individuals with NAFLD often exhibit altered lipid metabolism, which may affect oral microbiota composition, leading to dysbiosis and increased susceptibility to periodontal disease. Conversely, periodontitis has been linked to the progression of NAFLD through mechanisms involving systemic inflammation and oxidative stress. Chronic periodontal inflammation can release pro-inflammatory cytokines and bacterial toxins into the bloodstream, contributing to liver inflammation and exacerbating hepatic steatosis. Moreover, periodontitis-induced oxidative stress may promote hepatic lipid accumulation and IR, further aggravating NAFLD. The interplay between NAFLD and periodontitis underscores the importance of comprehensive management strategies targeting both conditions. Lifestyle modifications such as regular exercise, a healthy diet, and proper oral hygiene practices are crucial for preventing and managing these interconnected diseases. Additionally, interdisciplinary collaboration between hepatologists and periodontists is essential for optimizing patient care and improving outcomes in individuals with NAFLD and periodontitis.

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