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1.
Polymers (Basel) ; 16(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38732686

RESUMO

Polyvinylpyrrolidone (PVP) is a synthetic polymer that holds significance in various fields such as biomedical, medical, and electronics, due to its biocompatibility and exceptional dielectric properties. Electrospinning is the most commonly used tool to fabricate fibers because of its convenience and the wide choice of parameter optimization. Various parameters, including solution molarity, flow rate, voltage, needle gauge, and needle-to-collector distance, can be optimized to obtain the desired morphology of the fibers. Although PVP is commercially available in various molecular weights, PVP with a molecular weight of 130,000 g/mol is generally considered to be the easiest PVP to fabricate fibers with minimal challenges. However, the fiber diameter in this case is usually in the micron regime, which limits the utilization of PVP fibers in fields that require fiber diameters in the nano regime. Generally, PVP with a lower molecular weight, such as 10,000 g/mol and 55,000 g/mol, is known to present challenges in fiber preparation. In the current study, parameter optimization for PVP possessing molecular weights of 10,000 g/mol and 55,000 g/mol was carried out to obtain nanofibers. The electrospinning technique was utilized for fiber fabrication by optimizing the above-mentioned parameters. SEM analysis was performed to analyze the fiber morphology, and quantitative analysis was performed to correlate the effect of parameters on the fiber morphology. This research study will lead to various applications, such as drug encapsulation for sustained drug release and nanoparticles/nanotubes encapsulation for microwave absorption applications.

2.
Front Chem ; 12: 1380523, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694406

RESUMO

Diabetes mellitus is a multi-systematic chronic metabolic disorder and life-threatening disease resulting from impaired glucose homeostasis. The inhibition of glucosidase, particularly α-glucosidase, could serve as an effective methodology in treating diabetes. Attributed to the catalytic function of glucosidase, the present research focuses on the synthesis of sulfonamide-based acyl pyrazoles (5a-k) followed by their in vitro and in silico screening against α-glucosidase. The envisaged structures of prepared compounds were confirmed through NMR and FTIR spectroscopy and mass spectrometry. All compounds were found to be more potent against α-glucosidase than the standard drug, acarbose (IC50 = 35.1 ± 0.14 µM), with IC50 values ranging from 1.13 to 28.27 µM. However, compound 5a displayed the highest anti-diabetic activity (IC50 = 1.13 ± 0.06 µM). Furthermore, in silico studies revealed the intermolecular interactions of most potent compounds (5a and 5b), with active site residues reflecting the importance of pyrazole and sulfonamide moieties. This interaction pattern clearly manifests various structure-activity relationships, while the docking results correspond to the IC50 values of tested compounds. Hence, recent investigation reveals the medicinal significance of sulfonamide-clubbed pyrazole derivatives as prospective therapeutic candidates for treating type 2 diabetes mellitus (T2DM).

3.
Int J Rehabil Res ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38682376

RESUMO

Pain and somatosensory impairments are commonly reported following stroke. This study investigated the relationship between somatosensory impairments (touch detection, touch discrimination and proprioceptive discrimination) and the reported presence and perception of any bodily pain in stroke survivors. Stroke survivors with somatosensory impairment (N = 45) completed the Weinstein Enhanced Sensory Test (WEST), Tactile Discrimination Test, and Wrist Position Sense Test for quantification of somatosensation in both hands and the McGill Pain Questionnaire, visual analog scale and the Neuropathic Pain Symptom Inventory (NPSI) for reporting presence and perception of pain. No relationship was observed between somatosensory impairment (affected contralesional hand) of touch detection, discriminative touch or proprioceptive discrimination with the presence or perception of pain. However, a weak to moderate negative relationship between touch detection in the affected hand (WEST) and perception of pain intensity (NPSI) was found, suggesting that stroke survivors with milder somatosensory impairment of touch detection, rather than severe loss, are likely to experience higher pain intensity [rho = -0.35; 95% confidence interval (CI), -0.60 to -0.03; P = 0.03]. Further, a moderate, negative relationship was found specifically with evoked pain (NPSI) and touch detection in the affected hand (rho = -0.43; 95% CI, -0.72 to -0.02; P = 0.03). In summary, our findings indicate a weak to moderate, albeit still uncertain, association, which prevents making a definitive conclusion. Nevertheless, our findings contribute to our understanding of the complexities surrounding the experience of pain in survivors of stroke and provide direction for future studies.

4.
Brain ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38533783

RESUMO

Exposure to repetitive head impacts (RHIs) in contact sports is associated with neurodegenerative disorders including chronic traumatic encephalopathy (CTE) which currently can be diagnosed only at postmortem. American football players are at higher risk of developing CTE given their exposure to RHIs. One promising approach for diagnosing CTE in vivo is to explore known neuropathological abnormalities at postmortem in living individuals using structural magnetic resonance imaging (MRI). MRI brain morphometry was evaluated in 170 male former American football players ages 45-74 years (n = 114 professional; n = 56 college) and 54 same-age unexposed asymptomatic male controls (n = 58 age range 45-74). Cortical thickness and volume of regions of interest were selected based on established CTE pathology findings and were assessed using FreeSurfer. Group differences and interactions with age and exposure factors were evaluated using a generalized least squares model. A separate logistic regression and independent multinomial model were performed to predict each Traumatic Encephalopathy Syndrome (TES) diagnosis core clinical features and provisional level of certainty for CTE pathology using brain regions of interest. Former college and professional American football players (combined) showed significant cortical thickness and/or volume reductions compared to unexposed asymptomatic controls in the hippocampus amygdala entorhinal cortex parahippocampal gyrus insula temporal pole and superior frontal gyrus. Post-hoc analyses identified group-level differences between former professional players and unexposed asymptomatic controls in the hippocampus amygdala entorhinal cortex parahippocampal gyrus insula and superior frontal gyrus. Former college players showed significant volume reductions in the hippocampus amygdala and superior frontal gyrus compared to the unexposed asymptomatic controls. We did not observe age-by-group interactions for brain morphometric measures. Interactions between morphometry and exposure measures were limited to a single significant positive association between the age of first exposure to organized tackle football and right insular volume. We found no significant relationship between brain morphometric measures and the TES diagnosis core clinical features and provisional level of certainty for CTE pathology outcomes. These findings suggest that MRI morphometrics detects abnormalities in individuals with a history of RHI exposure that resemble the anatomic distribution of pathological findings from postmortem CTE studies. The lack of findings associating MRI measures with exposure metrics (except for one significant relationship) or TES diagnosis and core clinical features suggests that brain morphometry must be complemented by other types of measures to characterize individuals with RHIs.

5.
J Neuroinflammation ; 21(1): 46, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336728

RESUMO

BACKGROUND: Traumatic encephalopathy syndrome (TES) is defined as the clinical manifestation of the neuropathological entity chronic traumatic encephalopathy (CTE). A core feature of TES is neurobehavioral dysregulation (NBD), a neuropsychiatric syndrome in repetitive head impact (RHI)-exposed individuals, characterized by a poor regulation of emotions/behavior. To discover biological correlates for NBD, we investigated the association between biomarkers of inflammation (interleukin (IL)-1ß, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) in cerebrospinal fluid (CSF) and NBD symptoms in former American football players and unexposed individuals. METHODS: Our cohort consisted of former American football players, with (n = 104) or without (n = 76) NBD diagnosis, as well as asymptomatic unexposed individuals (n = 55) from the DIAGNOSE CTE Research Project. Specific measures for NBD were derived (i.e., explosivity, emotional dyscontrol, impulsivity, affective lability, and a total NBD score) from a factor analysis of multiple self-report neuropsychiatric measures. Analyses of covariance tested differences in biomarker concentrations between the three groups. Within former football players, multivariable linear regression models assessed relationships among log-transformed inflammatory biomarkers, proxies for RHI exposure (total years of football, cumulative head impact index), and NBD factor scores, adjusted for relevant confounding variables. Sensitivity analyses tested (1) differences in age subgroups (< 60, ≥ 60 years); (2) whether associations could be identified with plasma inflammatory biomarkers; (3) associations between neurodegeneration and NBD, using plasma neurofilament light (NfL) chain protein; and (4) associations between biomarkers and cognitive performance to explore broader clinical symptoms related to TES. RESULTS: CSF IL-6 was higher in former American football players with NBD diagnosis compared to players without NBD. Furthermore, elevated levels of CSF IL-6 were significantly associated with higher emotional dyscontrol, affective lability, impulsivity, and total NBD scores. In older football players, plasma NfL was associated with higher emotional dyscontrol and impulsivity, but also with worse executive function and processing speed. Proxies for RHI exposure were not significantly associated with biomarker concentrations. CONCLUSION: Specific NBD symptoms in former American football players may result from multiple factors, including neuroinflammation and neurodegeneration. Future studies need to unravel the exact link between NBD and RHI exposure, including the role of other pathophysiological pathways.


Assuntos
Lesões Encefálicas Traumáticas , Encefalopatia Traumática Crônica , Futebol Americano , Humanos , Idoso , Pessoa de Meia-Idade , Encefalopatia Traumática Crônica/patologia , Interleucina-6 , Biomarcadores
6.
Neurology ; 102(2): e208030, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38165330

RESUMO

BACKGROUND AND OBJECTIVES: Recent data link exposure to repetitive head impacts (RHIs) from American football with increased white matter hyperintensity (WMH) burden. WMH might have unique characteristics in the context of RHI beyond vascular risk and normal aging processes. We evaluated biological correlates of WMH in former American football players, including markers of amyloid, tau, inflammation, axonal injury, neurodegeneration, and vascular health. METHODS: Participants underwent clinical interviews, MRI, and lumbar puncture as part of the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project. Structural equation modeling tested direct and indirect effects between log-transformed total fluid-attenuated inversion recovery (FLAIR) lesion volumes (TLV) and the revised Framingham stroke risk profile (rFSRP), MRI-derived global metrics of cortical thickness and fractional anisotropy (FA), and CSF levels of amyloid ß1-42, p-tau181, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and neurofilament light. Covariates included age, race, education, body mass index, APOE ε4 carrier status, and evaluation site. Models were performed separately for former football players and a control group of asymptomatic men unexposed to RHI. RESULTS: In 180 former football players (mean age = 57.2, 36% Black), higher log(TLV) had direct associations with the following: higher rFSRP score (B = 0.26, 95% CI 0.07-0.40), higher p-tau181 (B = 0.17, 95% CI 0.01-0.43), lower FA (B = -0.28, 95% CI -0.42 to -0.13), and reduced cortical thickness (B = -0.25, 95% CI -0.45 to -0.08). In 60 asymptomatic unexposed men (mean age = 59.3, 40% Black), there were no direct effects on log(TLV) (rFSRP: B = -0.03, 95% CI -0.48 to 0.57; p-tau181: B = -0.30, 95% CI -1.14 to 0.37; FA: B = -0.07, 95% CI -0.48 to 0.42; or cortical thickness: B = -0.28, 95% CI -0.64 to 0.10). The former football players showed stronger associations between log(TLV) and rFSRP (1,069% difference in estimates), p-tau181 (158%), and FA (287%) than the unexposed men. DISCUSSION: Risk factors and biological correlates of WMH differed between former American football players and asymptomatic unexposed men. In addition to vascular health, p-tau181 and diffusion tensor imaging indices of white matter integrity showed stronger associations with WMH in the former football players. FLAIR WMH may have specific risk factors and pathologic underpinnings in RHI-exposed individuals.


Assuntos
Futebol Americano , Substância Branca , Masculino , Humanos , Pessoa de Meia-Idade , Peptídeos beta-Amiloides , Imagem de Tensor de Difusão , Substância Branca/diagnóstico por imagem , Fatores de Risco , Biomarcadores
7.
Int J Health Sci (Qassim) ; 18(1): 24-28, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38188899

RESUMO

Objective: The number of extremely drug-resistant (XDR) Salmonella typhi isolates is growing in the northwest of Pakistan, where health-care facilities are already under strain due to the coronavirus disease 2019 (COVID-19) issue. In Khyber Pakhtunkhwa, Pakistan, we currently describe the first widespread appearance of an XDR Salmonella typhi epidemic during the COVID-19 pandemic. This strain of Salmonella typhi is resistant to all first- and second-line drugs and even the third-generation cephalosporin. Methods: Salmonella species isolated from pediatric blood samples shown a high level of resistance to the various antibiotic classes evaluated between November and December 2020. Gender, age, address, and clinical symptoms were among the demographic information that was recorded. A total of 562 blood cultures from symptomatic patients have been collected by the Pathology Laboratory at a tertiary care institution of Rehman Medical Institute, Peshawar. All samples have been processed in accordance with regulatory requirements and incubated in BacT/ALERT 3D. Results: Of the 562 blood samples, 71 included Salmonella typhi, of which 66 (92.9%) and 5 (7%) were multidrug resistant (MDR) and XDR, respectively. Ciprofloxacin (100%), chloramphenicol (100%), ceftriaxone (100%), ampicillin (100%), and cotrimoxazole (93%) were completely resistant to all isolates. Azithromycin and carbapenems were effective against every Salmonella typhi isolate that was MDR or XDR. Males (76%) were more commonly affected than females (24%), and the frequency was substantially higher in children under 15 years of age (88%) than in adults (P = 0.0016). Conclusion: The emergence of XDR Salmonella typhi with a high level of resistance is in fact alarming. Due to the lack of viable treatment alternatives, the current situation necessitates the immediate implementation of efficient preventive measures, such as campaigns for typhoid vaccination and food and water safety.

8.
Medicina (Kaunas) ; 59(9)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37763767

RESUMO

Doppler findings of persistent reverse end-diastolic flow (PREDF) in a fetal middle cerebral artery (MCA) are a very rare sonographic finding and are a marker of poor fetal condition. This finding often leads to intrauterine fetal death or early neonatal death. Reverse end-diastolic flow in the middle cerebral artery is an advanced hemodynamic event. Fetal cerebral circulation normally has a high impedance; in the event of fetal hypoxemia, impedance decreases, resulting in the central redistribution of blood flow to vital organs, which maintains the oxygen delivery to the brain. Reverse flow in the middle cerebral arteries describes the loss of this autoregulatory process. PREDF is a sequence that occurs due to increased extracranial or intracranial pressure. Previous case reports mentioned intracranial hemorrhage, fetal growth restriction, fetal anemia, and fetal hepatic abnormalities as problems leading to PREDF. This condition presumably arises due to cerebral edema associated with severe hypoxemia. We reported Doppler findings of PREDF MCA in a 33-year-old female patient at 30 weeks gestation who was referred to the hospital with severe preeclampsia accompanied by fetal growth restriction and oligohydramnios. A cesarean section was performed due to severe preeclampsia and a low bishop score. Hypotheses on various etiologies and their association with intrauterine/neonatal death as well as the best management still require further investigation.


Assuntos
Morte Perinatal , Pré-Eclâmpsia , Recém-Nascido , Gravidez , Humanos , Feminino , Adulto , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiologia , Retardo do Crescimento Fetal , Cesárea , Morte Fetal , Ultrassonografia Pré-Natal/métodos , Velocidade do Fluxo Sanguíneo
9.
Polymers (Basel) ; 15(18)2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37765691

RESUMO

Innovation in biomedical science is always a field of interest for researchers. Drug delivery, being one of the key areas of biomedical science, has gained considerable significance. The utilization of simple yet effective techniques such as electrospinning has undergone significant development in the field of drug delivery. Various polymers such as PEG (polyethylene glycol), PLGA (Poly(lactic-co-glycolic acid)), PLA(Polylactic acid), and PCA (poly(methacrylate citric acid)) have been utilized to prepare electrospinning-based drug delivery systems (DDSs). Polyvinyl alcohol (PVA) has recently gained attention because of its biocompatibility, biodegradability, non-toxicity, and ideal mechanical properties as these are the key factors in developing DDSs. Moreover, it has shown promising results in developing DDSs individually and when combined with natural and synthetic polymers such as chitosan and polycaprolactone (PCL). Considering the outstanding properties of PVA, the aim of this review paper was therefore to summarize these recent advances by highlighting the potential of electrospun PVA for drug delivery systems.

10.
Int J Biol Macromol ; 253(Pt 2): 126813, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37690650

RESUMO

Antibacterial, durable and smart cotton fabrics was developed using chitosan-based formulation. The cellulose was covalently cross-linked with chitosan using TEOF. The antibacterial activity of prepared smart fabrics and CS was studied against S. aureus and E. coli strains. The FTIR, SEM and XRD were employed to confirm the linkage of CS molecules with cellulose in cotton fabrics. The CS of 160 KDa extracted from shrimp shell showed the optimum antibacterial activity. The prominent asymmetric, symmetric alkyl CH peaks of CS were shifted to 2930 and 2845 (cm-1), respectively. Moreover, the shifted peaks at 1590 and 1400 (cm-1) indicate the CO stretching and NH2 bending bands of CS, respectively. This confirm the existence of new imine functional group that was generated after cross-linking of NH2 groups of CS. The SEM results showed more uniform morphology of TEOF cross-linked fabrics versus CS coated fabrics, which revealed a promising microbial growth inhibition activity. The TEOF as a cross-linker has been unveiled, showcasing the effectiveness of this innovative crosslinking approach. The fabric treated with cross-linked CS exhibited remarkable antibacterial properties that endured even after undergoing 30 washing cycles. These antibacterial textiles possess substantial commercial potential across a diverse range of industries.


Assuntos
Quitosana , Fibra de Algodão , Celulose , Escherichia coli , Staphylococcus aureus , Têxteis , Antibacterianos/farmacologia
11.
RSC Adv ; 13(36): 24988-25001, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37614781

RESUMO

A series of ten novel compounds were synthesized by incorporating a 1,3 thiazole core into amantadine and their structures were validated using different analytical and spectral methods such as FTIR, EI-MS, 1H NMR, and 13C NMR. The antibacterial and enzyme inhibitory properties of these newly synthesized compounds were evaluated. Remarkably, the compounds exhibited significant antibacterial activity against Escherichia coli and Bacillus subtilis. Additionally, the in vitro inhibitory activities of the synthesized compounds, against α-amylase, α-glucosidase, and urease were investigated. Among the tested compounds, compound 6d demonstrated potent and selective inhibition of α-amylase IC50 = 97.37 ± 1.52 µM, while acarbose was used as positive control and exhibited IC50 = 5.17 ± 0.25 µM. Compound 6d and 6e exhibited prominent inhibition against α-glucosidase IC50 = 38.73 ± 0.80 µM and 41.63 ± 0.26 µM respectively. Furthermore, compound 6d inhibited urease with exceptional efficacy IC50 = 32.76 µM, while positive control thiourea showed more prominent activity having IC50 = 1.334 µM. Molecular docking studies disclosed the binding mechanism and affinity of these new inhibitors within the binding sites of various amino acids. To investigate the association between molecular structural characteristics and inhibitory actions of synthesized derivatives, preliminary structure-activity relationship (SAR) studies were performed. These findings indicated that compounds 6a, 6c, 6d and 6e are potential candidates for hit-to-lead follow-up in the drug-discovery process for treating diabetes and hyperglycemia.

12.
J Alzheimers Dis ; 93(3): 1181-1193, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37182888

RESUMO

BACKGROUND: Patients with eye disease have an increased risk for developing neurodegenerative disease. Neurodegenerative proteins can be measured in the eye; however, correlations between biomarker levels in eye fluid and neuropathological diagnoses have not been established. OBJECTIVE: This exploratory, retrospective study examined vitreous humor from 41 postmortem eyes and brain tissue with neuropathological diagnoses of Alzheimer's disease (AD, n = 7), chronic traumatic encephalopathy (CTE, n = 15), both AD + CTE (n = 10), and without significant neuropathology (controls, n = 9). METHODS: Protein biomarkers i.e., amyloid-ß (Aß40,42), total tau (tTau), phosphorylated tau (pTau181,231), neurofilament light chain (NfL), and eotaxin-1 were quantitatively measured by immunoassay. Non-parametric tests were used to compare vitreous biomarker levels between groups. Spearman's rank correlation tests were used to correlate biomarker levels in vitreous and cortical tissue. The level of significance was set to α= 0.10. RESULTS: In pairwise comparisons, tTau levels were significantly increased in AD and CTE groups versus controls (p = 0.08 for both) as well as AD versus AD+CTE group and CTE versus AD+CTE group (p = 0.049 for both). Vitreous NfL levels were significantly increased in low CTE (Stage I/II) versus no CTE (p = 0.096) and in low CTE versus high CTE stage (p = 0.03). Vitreous and cortical tissue levels of pTau 231 (p = 0.02, r = 0.38) and t-Tau (p = 0.04, r = -0.34) were significantly correlated. CONCLUSION: The postmortem vitreous humor biomarker levels significantly correlate with AD and CTE pathology in corresponding brains, while vitreous NfL was correlated with the CTE staging. This exploratory study indicates that biomarkers in the vitreous humor may serve as a proxy for neuropathological disease.


Assuntos
Doença de Alzheimer , Encefalopatia Traumática Crônica , Doenças Neurodegenerativas , Humanos , Doença de Alzheimer/metabolismo , Encefalopatia Traumática Crônica/patologia , Doenças Neurodegenerativas/metabolismo , Estudos Retrospectivos , Corpo Vítreo/metabolismo , Encéfalo/patologia , Proteínas tau/metabolismo , Peptídeos beta-Amiloides/metabolismo , Biomarcadores/metabolismo
13.
Molecules ; 28(10)2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37241836

RESUMO

The tropylium ion is a non-benzenoid aromatic species that works as a catalyst. This chemical entity brings about a large number of organic transformations, such as hydroboration reactions, ring contraction, the trapping of enolates, oxidative functionalization, metathesis, insertion, acetalization, and trans-acetalization reactions. The tropylium ion also functions as a coupling reagent in synthetic reactions. This cation's versatility can be seen in its role in the synthesis of macrocyclic compounds and cage structures. Bearing a charge, the tropylium ion is more prone to nucleophilic/electrophilic reactions than neutral benzenoid equivalents. This ability enables it to assist in a variety of chemical reactions. The primary purpose of using tropylium ions in organic reactions is to replace transition metals in catalysis chemistry. It outperforms transition-metal catalysts in terms of its yield, moderate conditions, non-toxic byproducts, functional group tolerance, selectivity, and ease of handling. Furthermore, the tropylium ion is simple to synthesize in the laboratory. The current review incorporates the literature reported from 1950 to 2021; however, the last two decades have witnessed a phenomenal upsurge in the utilization of the tropylium ion in the facilitation of organic conversions. The importance of the tropylium ion as an environmentally safe catalyst in synthesis and a comprehensive summary of some important reactions catalyzed via tropylium cations are described.

14.
Molecules ; 28(5)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36903376

RESUMO

Alzheimer's disease (AD) is one of the progressive neurological disorders and the main cause of dementia all over the world. The multifactorial nature of Alzheimer's disease is a reason for the lack of effective drugs as well as a basis for the development of new structural leads. In addition, the appalling side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with the marketed treatment modalities and many failed clinical trials significantly limit the use of drugs and alarm for a detailed understanding of disease heterogeneity and the development of preventive and multifaceted remedial approach desperately. With this motivation, we herein report a diverse series of piperidinyl-quinoline acylhydrazone therapeutics as selective as well as potent inhibitors of cholinesterase enzymes. Ultrasound-assisted conjugation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes (4a,b) and (un)substituted aromatic acid hydrazides (7a-m) provided facile access to target compounds (8a-m and 9a-j) in 4-6 min in excellent yields. The structures were fully established using spectroscopic techniques such as FTIR, 1H- and 13C NMR, and purity was estimated using elemental analysis. The synthesized compounds were investigated for their cholinesterase inhibitory potential. In vitro enzymatic studies revealed potent and selective inhibitors of AChE and BuChE. Compound 8c showed remarkable results and emerged as a lead candidate for the inhibition of AChE with an IC50 value of 5.3 ± 0.51 µM. The inhibitory strength of the optimal compound was 3-fold higher compared to neostigmine (IC50 = 16.3 ± 1.12 µM). Compound 8g exhibited the highest potency and inhibited the BuChE selectively with an IC50 value of 1.31 ± 0.05 µM. Several compounds, such as 8a-c, also displayed dual inhibitory strength, and acquired data were superior to the standard drugs. In vitro results were further supported by molecular docking analysis, where potent compounds revealed various important interactions with the key amino acid residues in the active site of both enzymes. Molecular dynamics simulation data, as well as physicochemical properties of the lead compounds, supported the identified class of hybrid compounds as a promising avenue for the discovery and development of new molecules for multifactorial diseases, such as Alzheimer's disease (AD).


Assuntos
Doença de Alzheimer , Quinolinas , Humanos , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/química , Simulação de Acoplamento Molecular , Acetilcolinesterase/metabolismo , Colinesterases/metabolismo , Quinolinas/uso terapêutico , Relação Estrutura-Atividade , Estrutura Molecular
15.
Ann N Y Acad Sci ; 1522(1): 139-148, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36924008

RESUMO

Adolescent motherhood has been linked with poor health outcomes at birth for children, including high neonatal mortality, low birthweight, and small-for-gestational-age rates. However, longer-term growth outcomes in the children of adolescent mothers in low-resource settings remain inadequately studied. We used longitudinal data from the India Human Development Surveys, 2004-2005 and 2011-2012 (n = 12,182) and employed regression and propensity score matching analysis to compare the following growth indicators of children born to adolescent mothers (ages 19 years or below) with those born to older mothers. Growth indicators included height and weight during ages 0-5 years and 6-12 years and change in height and weight between the two periods. In regression-based estimates, children born to adolescent mothers were 0.01 m shorter and weighed 0.2 kg less than children of older mothers at ages 0-5 years. At ages 6-12 years, those born to adolescent mothers were 0.02 m shorter and weighed 0.97 kg less. The height difference between the two groups increased by 0.01 m and the weight difference grew by 0.77 kg over time. Height and weight difference between the two groups worsened among boys over time, while for girls, only the weight gap worsened. The results were similar when using propensity score matching methods. Public policies for reducing child marriage, combined with targeted health, nutrition, and well-being programs for adolescent mothers, are essential for both preventing adolescent childbearing and reducing its impact on growth failure among children in India.


Assuntos
Mães Adolescentes , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Feminino , Adolescente , Criança , Humanos , Adulto Jovem , Adulto , Lactente , Pré-Escolar , Recém-Nascido Pequeno para a Idade Gestacional , Mães , Estado Nutricional
16.
Ann Med Surg (Lond) ; 84: 104949, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36582906

RESUMO

Introduction: and importance: Foetal hydrocolpos and anorectal malformation are difficult to diagnose prenatally due to abundance of differential diagnoses. This case report presents the challenges of diagnosing such disorders. Case presentation: A G3P2A0 woman came at 32 weeks of pregnancy with a referral for foetal ovarian cyst. Ultrasound revealed a singleton breech pregnancy, estimated foetal weight 3528 g. A septate abdominal cyst measuring 11.31 × 7.17 cm and polyhydramnios were present. Elective caesarean section delivered a female baby weighing 2820 g and measuring 43 cm. Neonatal examination revealed a right lateral suprapubic mass and a rectovestibular fistula. A sinoscopy revealed a suspected hydrocolpos. An abdominal hydrocolpos drainage was performed; a patent urachus and normal bilateral adnexa were present. Clinical discussion: Hydrocolpos is a rare congenital disorder due to distal obstruction of various etiologies. It may be mistaken with other pathologies, including fetal ovarian cysts. A genitourinary congenital abnormality may occur in conjunction with other abnormalities, including gastrointestinal tract anomalies. The presence of imperforate anus and/or fistula should alert the clinician of a possible association with VACTERL syndrome. Conclusion: Hydrocolpos is a rare congenital genitourinary disorder with various differential diagnoses. Simultaneous presence of other abnormalities is likely, with possible association to other syndromes.

17.
Fed Pract ; 39(Suppl 2): S58-S61, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35929007

RESUMO

Background: Penile leiomyosarcoma arises from smooth muscles, which can be from dartos fascia, erector pili in the skin covering the shaft, or from tunica media of the superficial vessels and cavernosa. We describe presentation, treatment options, and recurrence pattern of this rare malignancy. Case Presentation: We present a case of penile leiomyosarcoma in a 70-year-old patient who presented to the urology clinic with 1-year history of a slowly enlarging penile mass associated with phimosis. Conclusions: Prognosis of penile LMS is difficult to ascertain because reported cases are rare. Penile leiomyosarcoma can be classified as superficial or deep based on tumor relation to tunica albuginea. Deep tumors (> 3 cm), high-grade lesions, and tumors with involvement of corpora cavernosa, tend to spread locally and metastasize to distant areas and require more radical surgery with or without postoperative radiation therapy. In contrast, superficial lesions can be treated with local excision only.

18.
Int J Behav Nutr Phys Act ; 19(1): 109, 2022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-36028890

RESUMO

BACKGROUND: Hip-worn accelerometer cut-points have poor validity for assessing children's sedentary time, which may partly explain the equivocal health associations shown in prior research. Improved processing/classification methods for these monitors would enrich the evidence base and inform the development of more effective public health guidelines. The present study aimed to develop and evaluate a novel computational method (CHAP-child) for classifying sedentary time from hip-worn accelerometer data. METHODS: Participants were 278, 8-11-year-olds recruited from nine primary schools in Melbourne, Australia with differing socioeconomic status. Participants concurrently wore a thigh-worn activPAL (ground truth) and hip-worn ActiGraph (test measure) during up to 4 seasonal assessment periods, each lasting up to 8 days. activPAL data were used to train and evaluate the CHAP-child deep learning model to classify each 10-s epoch of raw ActiGraph acceleration data as sitting or non-sitting, creating comparable information from the two monitors. CHAP-child was evaluated alongside the current practice 100 counts per minute (cpm) method for hip-worn ActiGraph monitors. Performance was tested for each 10-s epoch and for participant-season level sedentary time and bout variables (e.g., mean bout duration). RESULTS: Across participant-seasons, CHAP-child correctly classified each epoch as sitting or non-sitting relative to activPAL, with mean balanced accuracy of 87.6% (SD = 5.3%). Sit-to-stand transitions were correctly classified with mean sensitivity of 76.3% (SD = 8.3). For most participant-season level variables, CHAP-child estimates were within ± 11% (mean absolute percent error [MAPE]) of activPAL, and correlations between CHAP-child and activPAL were generally very large (> 0.80). For the current practice 100 cpm method, most MAPEs were greater than ± 30% and most correlations were small or moderate (≤ 0.60) relative to activPAL. CONCLUSIONS: There was strong support for the concurrent validity of the CHAP-child classification method, which allows researchers to derive activPAL-equivalent measures of sedentary time, sit-to-stand transitions, and sedentary bout patterns from hip-worn triaxial ActiGraph data. Applying CHAP-child to existing datasets may provide greater insights into the potential impacts and influences of sedentary time in children.


Assuntos
Comportamento Sedentário , Coxa da Perna , Acelerometria , Serviços de Saúde , Humanos , Projetos de Pesquisa
19.
J Surg Case Rep ; 2022(6): rjac303, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35774479

RESUMO

Intussusception in adults is a relatively uncommon occurrence for a cause of bowel obstruction, which can present acutely, chronically or in an acute on chronic fashion. It is clinically concerning because of the possibility of cancer acting as a lead point. Small bowel tumours are rare, mostly detected incidentally with small bowel obstruction. Inflammatory fibroid polyp (IFP) is a rare benign tumour of the small bowel, either detected incidentally on imaging or endoscopy carried out for other reasons, or presents with acute features. We present a case of small bowel intussusception caused by IFP within the distal third of the ileum as a leading point. The patient presented acutely with small bowel obstruction, on a background of recurrent non-specific abdominal pain over the preceding month, and the computed tomography scan revealed an intussusception that was timely managed with a laparoscopy-assisted small bowel segmental resection.

20.
Int J Behav Nutr Phys Act ; 19(1): 75, 2022 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-35761363

RESUMO

BACKGROUND: Older adults are the least active population in the U.S. Low-income communities have fewer physical activity (PA) resources, contributing to less PA and increased chronic disease risk. This study assessed the effect of the multilevel, peer-led, Peer Empowerment Program 4 Physical Activity (PEP4PA) on moderate-to-vigorous PA (MVPA) and health outcomes, over 2 years of follow up. METHODS: In a cluster-randomized controlled trial, 12 senior or community centers serving low-income older adults were assigned to a PA intervention (n = 6) or usual programming (n = 6) condition. PEP4PA included self-monitoring, health coaching, group walks, social support, and community advocacy to improve walking conditions. The primary outcome was daily minutes of MVPA (7-day accelerometer). Secondary outcomes included Perceived Quality of Life (PQoL), 6-Minute Walk Test (6-MWT), blood pressure (BP), and depressive symptoms at baseline, 6, 12, 18 and 24 months. Mixed effects regression models estimated the effects on outcomes between groups over time and included random effects for repeated measures and center clustering. Effect modification by sex and income status was assessed. We calculated the incremental cost per daily minute of MVPA gained in the intervention group relative to the control group to assess cost effectiveness. RESULTS: We enrolled 476 older adults (50 + years). Participants were on average 71 years old, 76% female, 60% low income, and 38% identified as racial or ethnic minorities. Compared to the control group, intervention participants sustained roughly a 10 min/day increase in MVPA from baseline at all time points and increased mean PQoL scores from unsatisfied at baseline to satisfied at 12, 18 and 24 months. Males and higher-income groups had greater improvements in MVPA. No significant effects were observed for 6-MWT or depressive symptoms, and BP results were mixed. The incremental cost per minute MVPA gained per person was $0.25, $0.09, $0.06, and $0.05 at 6, 12, 18 and 24 months, respectively. CONCLUSIONS: PEP4PA achieved increases in MVPA and PQoL in low-income older adults, over 2 years of follow up. The peer-led, community-based intervention provides a sustainable and cost-effective model to improve health behaviors in underserved, aging populations. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02405325 ) March 20, 2015.


Assuntos
Exercício Físico , Qualidade de Vida , Idoso , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pobreza , Caminhada
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