Commonly called the Mexican prickly poppy, Argemone mexicana is a stress-resistant member of the Papaveraceae family of plants that has been used in traditional medicine for centuries by indigenous ...communities in Mexico and Western parts of the United States. This plant has been exploited to treat a wide variety of ailments, with reported antimicrobial and antioxidant properties, as well as cytotoxic effects against some human cancer cell lines. Due to its various therapeutic uses and its abundance of secondary metabolites, A. mexicana has great potential as a drug discovery candidate. Herein, the germination conditions of A. mexicana are described and the cytotoxic activities of different parts (seeds, leaves, inner vs. outer roots) of the plant from methanol or hexane extracts are preliminarily characterized against cells of seven unique organisms. When comparing 1 mg of each sample normalized to background solvent alone, A. mexicana methanol outer root and leaf extracts possessed the strongest antimicrobial activity, with greatest effects against the Gram-positive bacteria tested, and less activity against the Gram-negative bacteria and fungi tested. Additionally, using the MTT colorimetric assay, the outer root methanol and seed hexane extracts displayed pronounced inhibitory effects against human colon cancer cells. Quantification of c-MYC (oncogene) and APC (tumor suppressor) mRNA levels help elucidate how the A. mexicana root methanol extract may be affecting colon cancer cells. After ultra-performance liquid chromatography coupled with mass spectrometry and subsequent nuclear magnetic resonance analysis of the root and leaf methanol fractions, two main antibacterial compounds, chelerythrine and berberine, have been identified. The roots were found to possess both phytocompounds, while the leaf lacked chelerythrine. These data highlight the importance of plants as an invaluable pharmaceutical resource at a time when antimicrobial and anticancer drug discovery has plateaued.
Pregnant women with epilepsy frequently experience seizures related to pregnancy complications and are often prescribed anti-epileptic drugs (AEDs) to manage their symptoms. However, less is known ...about the comparative safety of AED exposure in utero. We aimed to compare the risk of congenital malformations (CMs) and prenatal outcomes of AEDs in infants/children who were exposed to AEDs in utero through a systematic review and Bayesian random-effects network meta-analysis.
MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to December 15, 2015. Two reviewers independently screened titles/abstracts and full-text papers for experimental and observational studies comparing mono- or poly-therapy AEDs versus control (no AED exposure) or other AEDs, then abstracted data and appraised the risk of bias. The primary outcome was incidence of major CMs, overall and by specific type (cardiac malformations, hypospadias, cleft lip and/or palate, club foot, inguinal hernia, and undescended testes).
After screening 5305 titles and abstracts, 642 potentially relevant full-text articles, and 17 studies from scanning reference lists, 96 studies were eligible (n = 58,461 patients). Across all major CMs, many AEDs were associated with higher risk compared to control. For major CMs, ethosuximide (OR, 3.04; 95% CrI, 1.23-7.07), valproate (OR, 2.93; 95% CrI, 2.36-3.69), topiramate (OR, 1.90; 95% CrI, 1.17-2.97), phenobarbital (OR, 1.83; 95% CrI, 1.35-2.47), phenytoin (OR, 1.67; 95% CrI, 1.30-2.17), carbamazepine (OR, 1.37; 95% CrI, 1.10-1.71), and 11 polytherapies were significantly more harmful than control, but lamotrigine (OR, 0.96; 95% CrI, 0.72-1.25) and levetiracetam (OR, 0.72; 95% CrI, 0.43-1.16) were not.
The newer generation AEDs, lamotrigine and levetiracetam, were not associated with significant increased risks of CMs compared to control, and were significantly less likely to be associated with children experiencing cardiac malformations than control. However, this does not mean that these agents are not harmful to infants/children exposed in utero. Counselling is advised concerning teratogenic risks when the prescription is written for a woman of childbearing age and before women continue with these agents when considering pregnancy, such as switching from polytherapy to monotherapy with evidence of lower risk and avoiding AEDs, such as valproate, that are consistently associated with CMs. These decisions must be balanced against the need for seizure control.
PROSPERO CRD42014008925.
Elective surgeries can be associated with significant harm to older adults. The present study aimed to identify the prognostic factors associated with the development of postoperative complications ...among older adults undergoing elective surgery.
Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and AgeLine were searched for articles published between inception and April 21, 2016. Prospective studies reporting prognostic factors associated with postoperative complications (composite outcome of medical and surgical complications), functional decline, mortality, post-hospitalization discharge destination, and prolonged hospitalization among older adults undergoing elective surgery were included. Study characteristics and prognostic factors associated with the outcomes of interest were extracted independently by two reviewers. Random effects meta-analysis models were used to derive pooled effect estimates for prognostic factors and incidences of adverse outcomes.
Of the 5692 titles and abstracts that were screened for inclusion, 44 studies (12,281 patients) reported on the following adverse postoperative outcomes: postoperative complications (n =28), postoperative mortality (n = 11), length of hospitalization (n = 21), functional decline (n = 6), and destination at discharge from hospital (n = 13). The pooled incidence of postoperative complications was 25.17% (95% confidence interval (CI) 18.03-33.98%, number needed to follow = 4). The geriatric syndromes of frailty (odds ratio (OR) 2.16, 95% CI 1.29-3.62) and cognitive impairment (OR 2.01, 95% CI 1.44-2.81) were associated with developing postoperative complications; however, there was no association with traditionally assessed prognostic factors such as age (OR 1.07, 95% CI 1.00-1.14) or American Society of Anesthesiologists status (OR 2.62, 95% CI 0.78-8.79). Besides frailty, other potentially modifiable prognostic factors, including depressive symptoms (OR 1.77, 95% CI 1.22-2.56) and smoking (OR 2.43, 95% CI 1.32-4.46), were also associated with developing postoperative complications.
Geriatric syndromes are important prognostic factors for postoperative complications. We identified potentially modifiable prognostic factors (e.g., frailty, depressive symptoms, and smoking) associated with developing postoperative complications that can be targeted preoperatively to optimize care.
Aim
To determine the systemic inflammatory burden, including hsCRP and its monomeric forms, in patients with apical lesions of endodontic origin treated with root canal treatment (RCT).
Methodology
...Prospective pre‐/post‐study. Apical periodontitis (AP) individuals aged 16–40 were included (N = 29). Individuals received RCT and were followed at 1 and 6 months. Fasting blood samples were obtained. Apical lesions of endodontic origin (ALEO) diameter (mm), and periapical index (PAI), were recorded. The serum concentrations of total hsCRP were determined by turbidimetry. Tumour necrosis factor (TNF)‐α, interleukin (IL)‐6, IL‐10, IL‐1β, and soluble (s) E‐selectin were assessed by Multiplex assay. Additionally, mCRP forms were determined in the serum of AP patients with a baseline moderate to high cardiovascular risk based on hsCRP stratification (hsCRP ≥1 mg/L) by immunowestern blot (n = 15). Also, CRP isoforms were explored in ALEOs from AP individuals (n = 4). Data were analysed with StataV16.
Results
Periapical index and ALEO sizes were reduced at both follow‐up visits after RCT (p < .05). Serum levels of TNF‐α, IL‐6, IL‐10, IL‐1β, and sE‐selectin did not show significant differences. CRP was borderline reduced at 1 month (p = .04); however, in AP individuals at cardiovascular risk (hsCRP ≥ 1 mg/L), hsCRP and its monomeric isoform significantly decreased at 1 and 6 months (p < .05).
Conclusions
High‐sensitivity CRP and mCRP are reduced after RCT in AP individuals at cardiovascular risk.
Aim
The aim of this study was to assess the levels and diagnostic accuracy of a set of potential biomarkers of periodontal tissue metabolism in gingival crevicular fluid (GCF) from patients with ...chronic periodontitis (CP) and asymptomatic apical periodontitis ( AAP).
Materials and Methods
Thirty one GCF samples from 11 CP patients, 44 GCF samples from 38 AAP patients and 31 GCF samples from 13 healthy volunteers were obtained (N = 106). Matrix metalloproteinases (MMPs) ‐2 and ‐9 were determined by zymography; levels of MMP‐8 by ELISA and IFMA and MPO by ELISA. IL‐1, IL‐6, TNFα, DKK‐1, Osteonectin, Periostin, TRAP‐5 and OPG were determined by a multiplex quantitative panel. Statistical analysis was performed using linear mixed‐effects models.
Results
The MMP‐9 and MMP‐8 were higher in CP, followed by AAP, versus healthy individuals (p < 0.05). ProMMP‐2, MPO, IL‐1, IL‐6, PTN, TRAP‐5 and OPG were significantly higher in CP when compared with AAP and healthy patients (p < 0.05). The highest diagnostic accuracies were observed for ProMMP‐2, ProMMP‐9, MMP‐8 and TRAP‐5 (AUC > 0.97) in CP, and for the active form of MMP‐9 and MMP‐8 (AUC > 0.90) in AAP.
Conclusion
Gingival crevicular fluid composition is modified by CP and AAP. MMP‐9 and MMP‐8 show diagnostic potential for CP and AAP, whereas MMP‐2 and TRAP‐5 are useful only for CP.
ObjectivesCompare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding.Design and settingSystematic review and Bayesian ...random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers.Participants29 cohort studies including 5100 infants/children.InterventionsMonotherapy and polytherapy AEDs including first-generation (carbamazepine, clobazam, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproate) and newer-generation (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin) AEDs. Epileptic women who did not receive AEDs during pregnancy or breast feeding served as the control group.Primary and secondary outcome measuresCognitive developmental delay and autism/dyspraxia were primary outcomes. Attention-deficit hyperactivity disorder, language delay, neonatal seizures, psychomotor developmental delay and social impairment were secondary outcomes.ResultsThe NMA on cognitive developmental delay (11 cohort studies, 933 children, 18 treatments) suggested that among all AEDs only valproate was statistically significantly associated with more children experiencing cognitive developmental delay compared with control (OR=7.40, 95% credible interval (CrI) 3.00 to 18.46). The NMA on autism (5 cohort studies, 2551 children, 12 treatments) suggested that oxcarbazepine (OR 13.51, CrI 1.28 to 221.40), valproate (OR 17.29, 95% CrI 2.40 to 217.60), lamotrigine (OR 8.88, CrI 1.28 to 112.00) and lamotrigine+valproate (OR 132.70, CrI 7.41 to 3851.00) were associated with significantly greater odds of developing autism compared with control. The NMA on psychomotor developmental delay (11 cohort studies, 1145 children, 18 treatments) found that valproate (OR 4.16, CrI 2.04 to 8.75) and carbamazepine+phenobarbital+valproate (OR 19.12, CrI 1.49 to 337.50) were associated with significantly greater odds of psychomotor delay compared with control.ConclusionsValproate alone or combined with another AED is associated with the greatest odds of adverse neurodevelopmental outcomes compared with control. Oxcarbazepine and lamotrigine were associated with increased occurrence of autism. Counselling is advised for women considering pregnancy to tailor the safest regimen.Trial registration numberPROSPERO database (CRD42014008925).
Background/Objectives
To examine the comparative effectiveness and safety of cognitive enhancers for Alzheimer's disease (AD).
Design
Systematic review and Bayesian network metaanalysis (NMA).
...Setting
MEDLINE, EMBASE, Cochrane Library, CINAHL, Ageline (inception–March 2016).
Participants
Individuals with AD in randomized controlled trials (RCTs), quasi‐RCTs, and nonrandomized studies.
Intervention
Any combination of donepezil, rivastigmine, galantamine, or memantine.
Measurements
Two reviewers independently screened titles, s, and full‐texts; ed data; and appraised risk of bias.
Results
Twenty thousand three hundred forty‐three citations were screened, and 142 studies were included (110 RCTs, 21 non‐RCTs, 11 cohort studies). NMA found that donepezil (Mini‐Mental State Examination: mean difference (MD) = 1.39, 95% credible interval (CrI) = 0.53–2.24), donepezil+memantine (2.59, 95% CrI = 0.12–4.98), and transdermal rivastigmine (2.02, 95% CrI = 0.02–4.08) improved cognition more than placebo. NMA found that donepezil (Alzheimer's Disease Assessment Scale–cognitive: MD = −3.29, 95% CrI = −4.57 to −1.99) and galantamine (MD = −2.13, 95% CrI = −3.91 to −0.27) improved cognition more than placebo. NMA found that donepezil+memantine (MD = −5.23, 95% CrI = −8.72 to −1.56) improved behavior more than placebo. NMA found that donepezil (MD = −0.32, 95% CrI = −0.46 to −0.19), donepezil+memantine (MD = −0.57, 95% CrI = −0.95 to −0.21), oral rivastigmine (MD = −0.38, 95% CrI = −0.56 to −0.17), and galantamine (MD = −3.79, 95% CrI = −6.98 to −0.59) improved global status more than placebo. NMA found that galantamine decreased the odds of mortality (odds ratio = 0.56, 95% CrI = 0.36–0.87). No agent increased risk of serious adverse events, falls, or bradycardia. Some increased risk of headache (oral rivastigmine), diarrhea (oral rivastigmine, donepezil), nausea (oral rivastigmine, donepezil, galantamine), and vomiting (oral rivastigmine, donepezil, galantamine).
Conclusion
An exhaustive review of the literature involving 142 studies demonstrated that cognitive enhancers in general have minimal effects on cognition according to minimal clinically important difference and global ratings. The drugs appear safe, but this must be interpreted cautiously because trial participants may have less comorbidity and fewer adverse effects than those treated with these drugs in clinical practice.
Abstract Aim Apical periodontitis (AP) is the chronic inflammation of the periradicular tissues in response to root canal infection. Whilst AP has been linked with systemic inflammation and ...noncommunicable diseases, its potential association with nonalcoholic fatty liver disease (NAFLD) is unknown. We aimed to evaluate the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels as surrogate markers of hepatic injury, and the systemic inflammatory burden in otherwise healthy individuals with and without AP diagnosis. Methodology Cross‐sectional study. Individuals with AP ( n = 30) and healthy controls ( n = 29) were recruited. The number, mean diameter (mm) and periapical index of the apical lesions of endodontic origin (ALEO) were assessed. ALT and AST levels (pg/mL) were measured through enzyme‐linked immunosorbent assays. The serum levels of TNF‐α, IL‐4, IL‐9, IL‐10, IL‐17A and IL‐22 were evaluated by Multiplex assay. Inferential analysis was performed using t ‐test or Mann–Whitney tests according to data distribution and linear regression models. Data were analysed with StataV16 ( p < .05). Results ALT and AST levels were significantly higher in individuals with AP compared to controls ( p < .05). Serum inflammatory biomarkers showed no significant differences between the study groups. Bivariate and multivariate analyses confirmed that AP diagnosis was independently associated with ALT and AST elevations ( p < .05). Additionally, the number of ALEO positively influenced AST levels ( p = .002). IL‐22 on the other hand, was associated with reduced ALT levels ( p = .043). Conclusion AP is associated with higher serum hepatic transaminases ALT and AST, potentially contributing to NAFLD physiopathology in young adults.
Individuals with co-occurring hyperactivity disorder/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) can have complex presentations that may complicate diagnosis and treatment. There ...are established guidelines with regard to the identification and treatment of ADHD and ASD as independent conditions. However, ADHD and ASD were not formally recognised diagnostically as co-occurring conditions until the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) was published in 2013. Hence, awareness and understanding of both conditions when they co-occur is less established and there is little guidance in the clinical literature. This has led to uncertainty among healthcare practitioners when working with children, young people and adults who present with co-existing ADHD and ASD. The United Kingdom ADHD Partnership (UKAP) therefore convened a meeting of professional experts that aimed to address this gap and reach expert consensus on the topic that will aid healthcare practitioners and allied professionals when working with this complex and vulnerable population.
UK experts from multiple disciplines in the fields of ADHD and ASD convened in London in December 2017. The meeting provided the opportunity to address the complexities of ADHD and ASD as a co-occurring presentation from different perspectives and included presentations, discussion and group work. The authors considered the clinical challenges of working with this complex group of individuals, producing a consensus for a unified approach when working with male and female, children, adolescents and adults with co-occurring ADHD and ASD. This was written up, circulated and endorsed by all authors.
The authors reached a consensus of practical recommendations for working across the lifespan with males and females with ADHD and ASD. Consensus was reached on topics of (1) identification and assessment using rating scales, clinical diagnostic interviews and objective supporting assessments; outcomes of assessment, including standards of clinical reporting; (2) non-pharmacological interventions and care management, including psychoeducation, carer interventions/carer training, behavioural/environmental and Cognitive Behavioural Therapy (CBT) approaches; and multi-agency liaison, including educational interventions, career advice, occupational skills and training, and (3) pharmacological treatments.
The guidance and practice recommendations (Tables 1, 4, 5, 7, 8 and 10) will support healthcare practitioners and allied professionals to meet the needs of this complex group from a multidisciplinary perspective. Further research is needed to enhance our understanding of the diagnosis, treatment and management of individuals presenting with comorbid ADHD and ASD.
To assess challenges with daily oral antiretroviral therapy (ART), we analyzed data for 2389 participants in the 2019 Positive Perspectives survey of people living with HIV in 25 countries. ...ART-related challenges reported included difficulty swallowing pills (33.1% 790/2389); stress from daily dosing routine (33.3% 795/2389); bad memories from daily intake of HIV medication (35.1%839/2389), and concern “that having to take pills every day means a greater chance of revealing my HIV status to others” (37.9% 906/2389). Individuals who felt empowered by daily oral dosing “taking my pill(s) every day reassures me that my HIV is being kept under control” had 69% higher odds of optimal overall health (AOR 1.69, 95% CI 1.40–2.04). Conversely, odds of optimal overall health were lower among those who felt daily pill intake “limits my day-to-day life” (AOR 0.53, 95% CI 0.44–0.64). These findings show that there is need for increased flexibility of ART delivery to meet diverse patient needs.
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