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1.
Sci Prog ; 107(2): 368504241242276, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38614463

RESUMO

Objective: This pilot study assessed the effects of electronic noise-masking earbuds on subjective sleep perception and objective sleep parameters among healthcare workers (HCWs) reporting sleep difficulties during the COVID-19 pandemic. Methods: Using a pre-post design, 77 HCWs underwent 3 nights of baseline assessment followed by a 7-night intervention period. Participants wore an at-home sleep monitoring headband to assess objective sleep measures and completed subjective self-report assessments. The difference in mean sleep measures from baseline to intervention was estimated in linear mixed models. Results: Compared to baseline assessments, HCWs reported significant improvements in sleep quality as measured by the Insomnia Severity Index (ISI) (Cohen's d = 1.74, p < 0.001) and a significant reduction in perceived sleep onset latency (SOL) during the intervention (M = 17.2 minutes, SD = 7.7) compared to baseline (M = 24.7 minutes, SD = 16.1), (Cohen's d = -0.42, p = 0.001). There were no significant changes in objective SOL (p = 0.703). However, there was a significant interaction between baseline objective SOL (<20 minutes vs >20 minutes) and condition (baseline vs intervention) (p = 0.002), such that individuals with objective SOL >20 minutes experienced a significant decrease in objective SOL during the intervention period compared to baseline (p = 0.015). Conclusions: HCWs experienced a significant improvement in perceived SOL and ISI scores after using the electronic noise-masking earbuds. Our data provide preliminary evidence for a nonpharmacological intervention to improve the sleep quality of HCWs which should be confirmed by future controlled studies.


Assuntos
Pandemias , Sono , Humanos , Projetos Piloto , Tecnologia , Eletrônica , Pessoal de Saúde
2.
Malays J Med Sci ; 31(1): 1-13, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38456111

RESUMO

The coming years are likely to be turbulent due to a myriad of factors or polycrisis, including an escalation in climate extremes, emerging public health threats, weak productivity, increases in global economic instability and further weakening in the integrity of global democracy. These formidable challenges are not exogenous to the economy but are in some cases generated by the system itself. They can be overcome, but only with far-reaching changes to global economics. Our current socio-economic paradigm is insufficient for addressing these complex challenges, let alone sustaining human development, well-being and happiness. To support the flourishing of the global population in the age of polycrisis, we need a novel, person-centred and collective paradigm. The brain economy leverages insights from neuroscience to provide a novel way of centralising the human contribution to the economy, how the economy in turn shapes our lives and positive feedbacks between the two. The brain economy is primarily based on Brain Capital, an economic asset integrating brain health and brain skills, the social, emotional, and the diversity of cognitive brain resources of individuals and communities. People with healthy brains are essential to navigate increasingly complex systems. Policies and investments that improve brain health and hence citizens' cognitive functions and boost brain performance can increase productivity, stimulate greater creativity and economic dynamism, utilise often underdeveloped intellectual resources, afford social cohesion, and create a more resilient, adaptable and sustainability-engaged population.

3.
Respir Res ; 24(1): 221, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700291

RESUMO

BACKGROUND: Although asthma and chronic obstructive pulmonary disease (COPD) are two distinct chronic airway inflammatory diseases, they often co-exist in a patient and the condition is referred to as asthma-COPD overlap (ACO). Lack of evidence regarding the inflammatory cells in ACO airways has led to their poor prognosis and treatment. The objective of this endobronchial biopsy (EBB) study was to enumerate inflammatory cellular changes in the airway wall of ACO compared with asthma, COPD current smokers (CS) and ex-smokers (ES), normal lung function smokers (NLFS), and non-smoker controls (HC). METHODS: EBB tissues from 74 patients were immunohistochemically stained for macrophages, mast cells, eosinophils, neutrophils, CD8+ T-cells and CD4+ T-cells. The microscopic images of stained tissues were evaluated in the epithelium, reticular basement membrane (RBM) cells/mm RBM length, and lamina propria (LP) cells/mm2 up to a depth of 120 µM using the image analysis software Image-Pro Plus 7.0. The observer was blinded to the images and disease diagnosis. Statistical analysis was performed using GraphPad Prism v9. RESULTS: The tissue macrophages in ACO were substantially higher in the epithelium and RBM than in HC (P < 0.001 for both), COPD-ES (P < 0.001 for both), and -CS (P < 0.05 and < 0.0001, respectively). The ACO LP macrophages were significantly higher in number than COPD-CS (P < 0.05). The mast cell numbers in ACO were lower than in NLFS (P < 0.05) in the epithelium, lower than COPD (P < 0.05) and NLFS (P < 0.001) in RBM; and lower than  HC (P < 0.05) in LP. We noted lower eosinophils in ACO LP than HC (P < 0.05) and the lowest neutrophils in both ACO and asthma. Furthermore, CD8+ T-cell numbers increased in the ACO RBM than HC (P < 0.05), COPD-ES (P < 0.05), and NLFS (P < 0.01); however, they were similar in number in epithelium and LP across groups. CD4+ T-cells remained lower in number across all regions and groups. CONCLUSION: These results suggest that the ACO airway tissue inflammatory cellular profile differed from the contributing diseases of asthma and COPD with a predominance of macrophages.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Broncoscopia , Biópsia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Asma/diagnóstico , Pulmão
4.
ChemMedChem ; 18(6): e202200572, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36617507

RESUMO

Compounds containing arylpyrrole-, 1,2,4-triazole- and hydrazone structural frameworks have been widely studied and demonstrated to exhibit a wide range of pharmacological properties. Herein, an exploratory series of new 1,2,4-triazole derivatives designed by amalgamation of arylpyrrole and 1,2,4-triazole structural units via a hydrazone linkage is reported. The synthesised compounds were tested in vitro for their potential activity against Mycobacterium tuberculosis (MTB) H37 Rv strain. The most promising compound 13 - the derivative without the benzene ring appended to the pyrrole unit displayed acceptable activity (MIC90 =3.99 µM) against MTB H37 Rv, while other compounds from the series exhibited modest to weak antimycobacterial activity with MIC90 values in the range between 7.0 and >125 µM. Furthermore, in silico results, predicated using the SwissADME web tool, show that the prepared compounds display desirable ADME profile with parameters within acceptable range.


Assuntos
Antituberculosos , Mycobacterium tuberculosis , Antituberculosos/farmacologia , Antituberculosos/química , Triazóis/farmacologia , Triazóis/química , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade
5.
Fertil Steril ; 119(3): 364-374, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36702342

RESUMO

Over 2 decades of research indicate the significance of racial or ethnic disparities in mental illness in the United States. However, minoritized racial or ethnic groups tend to report overall lower prevalence rates of psychiatric disorders than White adults, although this varies depending on gender and race or ethnicity. We conducted a rigorous and systematic narrative synthesis on the differences in the prevalence rates and symptoms that differ across racial or ethnic women in depression, anxiety, eating disorders, and premenstrual syndrome or premenstrual dysphoric disorder. Seven systematic reviews and meta-analyses that examined racial/ethnic differences in depression and eating disorders were included. No review that examined racial/ethnic differences in anxiety or premenstrual syndrome or premenstrual dysphoric disorder met inclusion criteria. Methodological quality of the reviews, which was determined by the Assessment of Multiple Systematic Reviews criteria, revealed that the results of 5 reviews were rated as critically low confidence, one review was rated as low confidence, and one review was rated as high confidence. Findings were inconsistent across systematic reviews and meta-analyses because of the methodological differences in the original studies. Overall, racially or ethnically minoritized women generally report lower prevalence rates in depressive and eating disorders than the White women; however, they exhibit different or greater symptom presentation that could influence prevalence estimates depending on the diagnostic criteria followed. Methodological considerations are provided to strengthen the literature on racial or ethnic mental health disparities in women.


Assuntos
Saúde Mental , Transtorno Disfórico Pré-Menstrual , Adulto , Feminino , Humanos , Estados Unidos/epidemiologia , Revisões Sistemáticas como Assunto , Etnicidade , Saúde da Mulher
6.
Arch Pharm (Weinheim) ; 356(3): e2200409, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36446720

RESUMO

Herein we report the synthesis of 21 novel small molecules inspired by metronidazole and Schiff base compounds. The compounds were evaluated against Trichomonas vaginalis and cross-screened against other pathogenic protozoans of clinical relevance. Most of these compounds were potent against T. vaginalis, exhibiting IC50 values < 5 µM. Compound 20, the most active compound against T. vaginalis, exhibited an IC50 value of 3.4 µM. A few compounds also exhibited activity against Plasmodium falciparum and Trypanosomal brucei brucei, with compound 6 exhibiting an IC50 value of 0.7 µM against P. falciparum and compound 22 exhibiting an IC50 value of 1.4 µM against T.b. brucei. Compound 22 is a broad-spectrum antiprotozoal agent, showing activities against all three pathogenic protozoans under investigation.


Assuntos
Antiprotozoários , Malária Falciparum , Trichomonas vaginalis , Humanos , Metronidazol/farmacologia , Bases de Schiff/farmacologia , Relação Estrutura-Atividade , Antiprotozoários/farmacologia
7.
Chem Biodivers ; 19(11): e202200150, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36253138

RESUMO

Previous research shows that the root and bark extracts of Euclea natalensis have antiplasmodial activity, but the leaves have not been examined yet. This study investigated the phytochemical, antiplasmodial, and cytotoxic properties of the plant leaves. The activity against 3D7 Plasmodium falciparum was determined using the parasite lactate dehydrogenase assay, and the cytotoxicity against Vero and HeLa cells was evaluated using the MTT and resazurin assays, respectively. The bioactive compounds were isolated by chromatography, and their structures were established with spectroscopic and spectrometric techniques. The extract showed antiplasmodial activity (IC50 =25.6 µg/mL) and was not cytotoxic against Vero cells (IC50 =403.7 µg/mL). Purification of the extract afforded six flavonoid glycosides, four triterpenoids, and a coumarin. The glycosides showed antiplasmodial and cytotoxic activities, against HeLa cells, at 50 µg/mL, but the activity was reduced at 10 µg/mL. Naphthoquinones, which are among the predominant phytochemicals in the root and root bark of E. natalensis, were not detected in the leaves.


Assuntos
Antimaláricos , Ebenaceae , Humanos , Chlorocebus aethiops , Animais , Antimaláricos/farmacologia , Antimaláricos/química , Células HeLa , Células Vero , Extratos Vegetais/química , Ebenaceae/química , Folhas de Planta/química , Plasmodium falciparum , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/análise , Glicosídeos/análise
8.
ChemMedChem ; 17(22): e202200421, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36106757

RESUMO

A series of pyrrolo[2,3-d]pyrimidines were designed in silico as potential bumped kinase inhibitors targeting P. falciparum calcium dependent protein kinase 4 (PfCDPK4), with the potential to inhibit PfCDPK1 based on earlier studies of the two kinases. A small series of these compounds were prepared and assessed for inhibitory activity against PfCDPK4 and PfCDPK1 in vitro. Four of the compounds displayed promising inhibitory activity against either PfCDPK4 (IC50 =0.210-0.530 µM), or PfCDPK1 (IC50 =0.589 µM). These data will enable optimisation of the molecular model to better predict inhibitory activity against PfCDPK4.


Assuntos
Antimaláricos , Plasmodium falciparum , Inibidores de Proteínas Quinases , Aminas , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/enzimologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases/metabolismo , Pirimidinas/farmacologia , Relação Estrutura-Atividade , Antimaláricos/farmacologia
9.
Am J Physiol Lung Cell Mol Physiol ; 323(4): L473-L483, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35997281

RESUMO

Management of patients with asthma COPD overlap (ACO) is clinically challenging due to insufficient evidence of pathological changes in these patients. In this cross-sectional study, we evaluated airway remodeling in endobronchial biopsies from a total of 90 subjects, which included 12 ACO, 14 patients with asthma, 12 COPD exsmokers (ES), 11 current smokers (CS), 28 healthy controls (HC), and 13 normal lung function smokers (NLFS). Tissue was stained with Masson's trichrome. Epithelium, goblet cells, reticular basement membrane (RBM), cellularity, lamina propria (LP), and smooth muscle (SM) changes were measured using Image-Pro Plus v7 software. Differential airway remodeling pattern was seen in patients with ACO. A limited change was noted in the ACO epithelium compared with other pathological groups. RBM was substantially thicker in patients with ACO than in HC (P < 0.0002) and tended to be thicker than in patients with asthma and NLFS. The total RBM cells were higher in ACO than in the HC (P < 0.0001), COPD-CS (P = 0.0559), -ES (P = 0.0345), and NLFS (P < 0.0002), but did not differ from patients with asthma. Goblet cells were higher in the ACO than in the HC (P = 0.0028) and COPD-ES (P = 0.0081). The total LP cells in ACO appeared to be higher than in HC, COPD-CS, and NLFS but appeared to be lower than in patients with asthma. Finally, SM area was significantly lower in the ACO than in patients with asthma (P = 0.001), COPD-CS (=0.0290), and NLFS (P = 0.0011). This first comprehensive study suggests that patients with ACO had distinguishable tissue remodeling that appeared to be more severe than patients with asthma and COPD. This study will help in informed decision-making for better patient management in clinical practice.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Remodelação das Vias Aéreas , Estudos Transversais , Humanos , Doença Pulmonar Obstrutiva Crônica/patologia , Fumantes
10.
J Paediatr Child Health ; 58(8): 1407-1413, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35506702

RESUMO

AIM: Explore the prevalence of childhood anaphylaxis and clinical presentation of anaphylaxis in children across two regional emergency departments over a 7-year period. METHODS: Retrospective audit of all children (0-18 years) presenting to emergency from 1 January 2010 to 31 December 2016 with anaphylaxis, defined by Australasian Society of Clinical Immunology and Allergy definitions and doctor diagnosis. RESULTS: Seven hundred and twenty-four patients were identified with allergic diagnosis, 60% were diagnosed with non-anaphylaxis allergic reactions or unspecified urticaria and 40% with anaphylaxis (n = 286). Annual prevalence of anaphylaxis remained stable over the study period (M = 30.9/10 000 cases, range: 20.8-48.3/10 000). Gender distribution was equal, median age was 9.48 years (interquartile range = 4-15). Most (71%) arrived by private transport. 23% had a prior history of anaphylaxis. Food triggers (44%) were the most common cause of anaphylaxis. Insect bites/stings triggers occurred in 21%. Patients were promptly assessed (average wait time = 13 min), 16% received prior adrenaline injections. Adrenaline was administered in 26% and 20% were admitted to hospital. On discharge, 29% had a follow-up plan, 9% received an allergy clinic referral, 6% anaphylaxis action plan, 26% adrenaline autoinjector prescriptions and allergy testing performed in 6%. CONCLUSIONS: We found a relatively low prevalence of overall childhood anaphylaxis in a regional area. The two most common causes of anaphylaxis in this population (food and bites/stings) recorded increased prevalence providing an opportunity for further study. Significant gaps in evidence-based care of anaphylaxis were noted, demonstrating the need for improved recognition and treatment guideline implementation in regional areas.


Assuntos
Anafilaxia , Serviço Hospitalar de Emergência , Anafilaxia/diagnóstico , Anafilaxia/tratamento farmacológico , Anafilaxia/epidemiologia , Criança , Epinefrina/uso terapêutico , Humanos , Encaminhamento e Consulta , Estudos Retrospectivos
11.
Pharmaceuticals (Basel) ; 15(4)2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35455467

RESUMO

Vachellia xanthophloea is used in Zulu traditional medicine as an antimalarial remedy. A moderate antiplasmodial activity was previously reported for extracts of the plant against D10 Plasmodium falciparum. This study aimed to identify the phytochemicals responsible for the antiplasmodial activity of the leaf extract. The compounds were isolated by chromatography and their structures were determined using spectroscopic and spectrometric methods. The antiplasmodial activity was evaluated using a parasite lactate dehydrogenase assay and cytotoxicity was determined using a resazurin assay. The ethyl acetate fraction inhibited P. falciparum with IC50 = 10.6 µg/mL and showed minimal cytotoxicity (98% cell viability at 33 µg/mL). The chromatographic purification of this fraction afforded sixteen compounds, including two new flavonoids. A 1:1 mixture of phytol and lupeol was also isolated from the hexane fraction. All the compounds were reported from V. xanthophloea for the first time. Among the isolated metabolites, methyl gallate displayed the best activity against P. falciparum (IC50 = 1.2 µg/mL), with a 68% viability of HeLa cells at 10 µg/mL. Therefore, methyl gallate was responsible for the antiplasmodial activity of the V. xanthophloea leaf extract and its presence in the leaf extract might account for the folkloric use of the plant as an antimalarial remedy.

12.
World Allergy Organ J ; 15(2): 100632, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35280502

RESUMO

Background: Temperate grass (eg, ryegrass) pollen is a major driver of seasonal allergic rhinitis (SAR) and asthma risks, including thunderstorm asthma. Data for the effectiveness of temperate grass pollen allergen immunotherapy (AIT) in SAR patients from the southern hemisphere, who are frequently polysensitized to subtropical grass pollens, are limited. The 300 IR 5-grass pollen sublingual immunotherapy tablet (300 IR 5-grass SLIT) is known to be effective in polysensitized SAR patients with primary allergy to temperate grasses, however, the influence of polysensitization to subtropical grass pollen on treatment responses has yet to be specifically addressed. Key aims of this study were to measure patient treatment satisfaction during 300 IR 5-grass SLIT treatment and evaluate how polysensitization to subtropical grass pollens affects treatment responses. Methods: A prospective observational study was conducted in 63 patients (aged ≥5 years) in several temperate regions of Australia prescribed 300 IR 5-grass SLIT for SAR over 3 consecutive grass pollen seasons. Ambient levels of pollen were measured at representative sites. Patient treatment satisfaction was assessed using a QUARTIS questionnaire. Rhinoconjunctivitis Total Symptom Score (RTSS) and a Hodges-Lehmann Estimator analysis was performed to evaluate if polysensitization to subtropical grass pollen affected SAR symptom intensity changes during SLIT. Results: A diagnosis of ryegrass pollen allergy was nearly universal. There were 74.6% (47/63) polysensitized to subtropical and temperate grass pollens. There were 23.8% (15/63) monosensitized to temperate grass pollens. From the first pollen season, statistically significant improvements occurred in SAR symptoms compared with baseline in both monosensitized and polysensitized patients, particularly in those polysensitized (P = 0.0297). Improvements in SAR symptoms were sustained and similar in both groups in the second and third pollen seasons, reaching 70-85% improvement (P < 0.01). Polysensitized patients from both northerly and southerly temperate regions in Australia showed similar improvements. Grass pollen counts in both regions were consistently highest during springtime. Conclusions: 300 IR 5-grass SLIT is effective in a real-life setting in SAR patients in the southern hemisphere with primary allergy to temperate grass pollen and predominantly springtime grass pollen exposures. Importantly, SLIT treatment effectiveness was irrespective of the patient's polysensitization status to subtropical grass pollens.

13.
Nat Prod Res ; 36(16): 4052-4060, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34343036

RESUMO

Previous results indicated that the methanol extract of Gardenia thunbergia has antiplasmodial activity but no compounds have ever been isolated from the plant. Therefore, this study aimed to investigate the phytochemical and antiplasmodial properties of the plant. The methanol leaf extract of G. thunbergia inhibited Plasmodium falciparum at 50 µg/mL (> 80% inhibition) and was not cytotoxic against HeLa cells. Chromatographic purification of the extract afforded a new saponin and eight other known compounds. The saponin and two flavonoid glycosides displayed non-selective antiplasmodial activity at 50 µg/mL but the activities were diminished at 10 µg/mL. The presence of the isolated compounds in the leaf extract of G. thunbergia could account for the folkloric use of the plant in treating malaria.


Assuntos
Acanthaceae , Antimaláricos , Gardenia , Saponinas , Antimaláricos/farmacologia , Células HeLa , Humanos , Metanol , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta , Plasmodium falciparum
14.
J Small Anim Pract ; 63(3): 188-196, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34937128

RESUMO

OBJECTIVES: To assess the inter-rater agreement of corneal cytology findings in canine ulcerative keratitis by veterinary surgeons of different training levels and the agreement of corneal cytology with culture. MATERIALS AND METHODS: Dogs with progressive ulcerative keratitis were prospectively recruited for corneal cytology and culture. Corneal cytology slides were reviewed by veterinary surgeons of different training levels (three general practitioners, three ophthalmologists and three pathologists). The inter-rater agreement of cytology findings and agreement of cytology with culture was assessed using the kappa measure of agreement. RESULTS: The study included 145 corneal cytology samples from 143 dogs (145 eyes) with progressive ulcerative keratitis. Positive cultures were obtained from 81 of 145 (56%) eyes. The most commonly isolated pathogens were Streptococcus canis, Pseudomonas aeruginosa and Staphylococcus pseudintermedius. The results demonstrated increased inter-rater agreement of corneal cytology and increased agreement with culture with increased ocular pathology expertise (pathologists > ophthalmologists > general practitioners). CLINICAL SIGNIFICANCE: This study provides important information about the diagnostic value of corneal cytology in canine ulcerative keratitis and the most common pathogens involved in such cases in the UK. Based on the results of this study, cytology findings should be interpreted in conjunction with the expertise of the observer. For maximal pathogen identification, both cytology and culture should be considered.


Assuntos
Úlcera da Córnea , Doenças do Cão , Animais , Córnea/patologia , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/patologia , Úlcera da Córnea/veterinária , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Cães
15.
Eur J Med Chem ; 227: 113913, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34656043

RESUMO

Human African trypanosomiasis is a vector-borne tropical disease of African origin. Presently, due to human migration and climate change, the disease might present global health and economic burdens as current chemotherapy of trypanosomiasis remains a challenge due to limited existing drugs, which are of poor efficacy, cause severe adverse events and are very costly. Recently, Beteck and co-workers identified a small library of 1,3,6-substituted non-fluoroquinolones that showed moderate to weak trypanocidal activity without cytotoxic effects. The current study further explored SARs of the quinolone scaffold in search for more potent trypanocidal agents. Fifteen novel quinolone derivatives bearing a heteroarylidene moiety at positon-6 and varied chemical entities at positions -1 and -3 of the quinolone scaffold were synthesized and evaluated in vitro for antitrypanosomal activity. The compounds exhibit exceptionally good antitrypanosomal activity with IC50 values in the low-micromolar to sub-micromolar range (0.08-15.26 µM), with compound 6d being the most active having an IC50 value of 80 nM against T.b. brucei. Compounds in this study generally have molecular weight less than 600Da, ClogP value of 2-4 and a BBB score of 1-5, hence they could be potentially effective against both stages of trypanosomiasis.


Assuntos
Quinolonas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Animais , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Estrutura Molecular , Testes de Sensibilidade Parasitária , Quinolonas/síntese química , Quinolonas/química , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química , Células Vero
16.
RSC Med Chem ; 12(10): 1750-1756, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34778775

RESUMO

HPPK, which directly precedes DHPS in the folate biosynthetic pathway, is a promising but chronically under-exploited anti-microbial target. Here we report the identification of new S. enterica HPPK inhibitors, offering potential for new resistance circumventing S. enterica therapies as well as avenues for diversifying the current HPPK inhibitor space.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34831762

RESUMO

Maternal obesity in pregnancy, a growing health problem in Australia, adversely affects both mothers and their offspring. Gestational diabetes mellitus (GDM) is similarly associated with adverse pregnancy and neonatal complications. A low-risk digital medical record audit of antenatal and postnatal data of 2132 pregnant mothers who gave birth between 2016-2018 residing in rural-regional Tasmania was undertaken. An expert advisory group guided the research and informed data collection. Fifty five percent of pregnant mothers were overweight or obese, 43.6% gained above the recommended standards for gestational weight gain and 35.8% did not have an oral glucose tolerance test. The audit identified a high prevalence of obesity among pregnant women and low screening rates for gestational diabetes mellitus associated with adverse maternal and neonatal pregnancy outcomes. We conclude that there is a high prevalence of overweight and obesity among pregnant women in rural regional Tasmania. Further GDM screening rates are low, which require addressing.


Assuntos
Diabetes Gestacional , Obesidade Materna , Índice de Massa Corporal , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Sobrepeso , Gravidez , Resultado da Gravidez/epidemiologia , Tasmânia/epidemiologia
18.
Nanomaterials (Basel) ; 11(7)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34361169

RESUMO

Nanostructured metal mesh structures demonstrating excellent conductivity and high transparency are one of the promising transparent conducting electrode (TCE) alternatives for indium tin oxide (ITO). Often, these metal nanostructures are to be employed as hybrids along with a conducting filler layer to collect charge carriers from the network voids and to minimize current and voltage losses. The influence of filler layers on dictating the extent of such ohmic loss is complex. Here, we used a general numerical model to correlate the sheet resistance of the filler, lateral charge transport distance in network voids, metal mesh line width and ohmic losses in optoelectronic devices. To verify this correlation, we prepared gold or copper network electrodes with different line widths and different filler layers, and applied them as TCEs in perovskite solar cells. We show that the photovoltaic parameters scale with the hybrid metal network TCE properties and an Au-network or Cu-network with aluminum-doped zinc oxide (AZO) filler can replace ITO very well, validating our theoretical predictions. Thus, the proposed model could be employed to select an appropriate filler layer for a specific metal mesh electrode geometry and dimensions to overcome the possible ohmic losses in optoelectronic devices.

19.
Molecules ; 26(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34201912

RESUMO

Ethnobotanical surveys indicate that the Masai and Kikuyu in Kenya, the Venda in South Africa, and the Gumuz people of Ethiopia use Pappea capensis for the treatment of malaria. The present study aimed to investigate the phytochemical and antiplasmodial properties of the plant leaves. The bioactive compounds were isolated using chromatographic techniques. The structures were established using NMR, HRMS, and UV spectroscopy. Antiplasmodial activity of P. capensis leaf extract and isolated compounds against chloroquine-sensitive 3D7 P. falciparum was evaluated using the parasite lactate dehydrogenase assay. Cytotoxicity against HeLa (human cervix adenocarcinoma) cells was determined using the resazurin assay. The extract inhibited the viability of Plasmodium falciparum by more than 80% at 50 µg/mL, but it was also cytotoxic against HeLa cells at the same concentration. Chromatographic purification of the extract led to the isolation of four flavonoid glycosides and epicatechin. The compounds displayed a similar activity pattern with the extract against P. falciparum and HeLa cells. The results from this study suggest that the widespread use of P. capensis in traditional medicine for the treatment of malaria might have some merits. However, more selectivity studies are needed to determine whether the leaf extract is cytotoxic against noncancerous cells.


Assuntos
Antimaláricos , Apiaceae/química , Citotoxinas , Flavonoides , Malária Falciparum/tratamento farmacológico , Folhas de Planta/química , Plasmodium falciparum/crescimento & desenvolvimento , Antimaláricos/química , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Citotoxinas/química , Citotoxinas/isolamento & purificação , Citotoxinas/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Células HeLa , Humanos , Malária Falciparum/metabolismo
20.
Chem Biodivers ; 18(8): e2100240, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34081396

RESUMO

Ozoroa obovata (Oliv.) R. & A. Fern. var. obovata found in KwaZulu-Natal in South Africa was investigated for phytochemical constituents, and for antiplasmodial and cytotoxic effects. The plant leaves were collected from the University of KwaZulu-Natal (UKZN) arboretum on the Pietermaritzburg Campus, in March 2019. The inhibitory activity against 3D7 Plasmodium falciparum was determined using the parasite lactate dehydrogenase (pLDH) assay and cytotoxicity against HeLa cells was evaluated using the resazurin assay. The bioactive compounds were isolated by chromatographic purification and their structures were established with spectroscopic and spectrometric techniques. The plant leaf extract displayed significant antiplasmodial activity at 50 µg/mL and was also cytotoxic against HeLa cells. Chromatographic purification of the extract led to the isolation of two biflavonoids, four flavonoid glycosides, a steroid glycoside, and a megastigmene derivative. The compounds displayed antiplasmodial and antiproliferative activities at 50 µg/mL but the activity was substantially reduced at 10 µg/mL. The activities and compounds are being reported in O. obovata for the first time.


Assuntos
Anacardiaceae/química , Antimaláricos/farmacologia , Extratos Vegetais/química , Plasmodium falciparum/efeitos dos fármacos , Anacardiaceae/metabolismo , Antimaláricos/química , Antimaláricos/isolamento & purificação , Biflavonoides/química , Biflavonoides/isolamento & purificação , Biflavonoides/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Células HeLa , Humanos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Folhas de Planta/metabolismo
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