Paper-based potentiometric sensing devices modified with chemically reduced graphene oxide (CRGO) for trace level determination of pholcodine (opiate derivative drug)

Robust, reliable and cost-effective paper-based analytical device for potentiometric pholcodine (opiate derivative drug) ion sensing has been prepared and characterized. A printed pholcodinium (PHL)²⁺/5-nitrobarbiturate (NB)⁻ ion-association complex as a sensory material-based all-solid-state ion-selective electrode (ISE) on a chemically reduced graphene oxide (CRGO) solid-contact, and a printed all-solid-state Ag/AgCl reference electrode, has been combined on a hydrophobic paper substrate coated with fluorinated alkyl silane (CF₃(CF₂)₇CH₂CH₂SiCl₃, C^F₁₀). The sensors revealed a potentiometric slope of 28.7 ± 0.3 mV dec⁻¹ (R² = 0.9998) over a linear range starting from 2.0 × 10⁻⁷ M to 1.0 × 10⁻² M and a detection limit of 0.04 μg mL⁻¹. The repeatability and stability of the pholcodine paper-based sensor was found to be 2.32%. The RSD% (n = 6) was found to be 2.67% when using five different paper-based sensors. The sensor revealed an excellent selectivity towards PHL over dextromethorphan, codeine, ephedrine, carbinoxamine, caffeine, ketamine, and K⁺, Na⁺ and Ca²⁺ ions. It showed a good recovery (94–104%) for the determination of PHL in different artificial serum samples. The presented paper-based analytical device was successfully introduced for PHL determination in different pharmaceutical formulations (i.e. syrups and suspensions) containing pholcodine. The current work can be considered as a promising possible analytical tool to obtain cost-effective and disposable paper-based potentiometric sensing devices. These devices can be potentially manufacturable at large scales in pharmaceutical, clinical and forensic applications for opiate drug assessment.

Robust, reliable and cost-effective paper-based analytical device for potentiometric pholcodine (opiate derivative drug) ion sensing has been prepared and characterized.     

Locally advanced tongue squamous cell carcinoma in epidermolysis simplex bullosa patient: a therapeutic conundrum

Epidermolysis bullosa simplex (EBS) is a debilitating condition affecting the skin and mucous membranes that is characterised by frequent ulceration and blistering on trivial trauma. In EBS, oral cavity mucosal injuries lead to a high propensity for developing squamous cell carcinomas. Locally advanced tongue carcinoma arising in this background presents a challenging therapeutic conundrum. To our knowledge, this is the first case of aggressive locally advanced tongue carcinoma that has developed sporadically in a patient with EBS and no family history. Routine screening of oral mucosal lesions will lead to early detection and timely management of this debilitating condition.     

Patterns of attendances to the hospital emergency eye care service: a multicentre study in England

Background/ObjectivesTo characterise the patterns of presentation and diagnostic frequencies in Hospital Emergency Eye Care Services (HEECS) across 13 hospitals in England.MethodsRetrospective, cross-sectional, observational multi-centre (n = 13) study to assess HEECS attendances over a 28-day study period. Data derived included: number of consecutive attendances, patient demographics and diagnoses. Age and gender variations, the impact of day of the week on attendance patterns, diagnostic frequencies and estimates of the annual incidence and attendance rates were evaluated.ResultsA total of 17,667 patient (mean ± standard deviation age = 49.6 ± 21.8 years) attendances were identified with an estimated HEECS annual new attendance rate of 31.0 per 1,000 population. Significantly more females (53%) than males (47%) attended HEECS (p < 0.001). Female attendances were 13% higher in those ≥50 years of age. Weekends were associated with a significant reduction in attendances compared to weekdays (χ² = 6.94, p < 0.001). Among weekdays, Mondays and Fridays were associated with significantly higher attendances compared with midweek (χ² = 2.20, p = 0.032). Presenting pathologies involving the external eye, cornea and conjunctiva accounted for 28.6% of the caseload.ConclusionThis is the largest multicentre study assessing attendance patterns in HEECS in England. We have, for the first time, observed a “weekend effect” in relation to attendance to HEECS. Differences in health-seeking behaviour and lack of awareness of HEECS weekend services may be partly attributed to the differences observed. Our findings, along with the type of presentations, have the potential to guide commissioners with future planning of HEECS.Subject terms: Epidemiology, Epidemiology     

Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease

Chronic kidney disease (CKD) imposes a strong and independent risk for peripheral artery disease (PAD). While solutes retained in CKD patients (uremic solutes) inflict vascular damage, their role in PAD remains elusive. Here, we show that the dietary tryptophan-derived uremic solutes including indoxyl sulfate (IS) and kynurenine (Kyn) at concentrations corresponding to those in CKD patients suppress β-catenin in several cell types, including microvascular endothelial cells (ECs), inhibiting Wnt activity and proangiogenic Wnt targets in ECs. Mechanistic probing revealed that these uremic solutes downregulated β-catenin in a manner dependent on serine 33 in its degron motif and through the aryl hydrocarbon receptor (AHR). Hindlimb ischemia in adenine-induced CKD and IS solute–specific mouse models showed diminished β-catenin and VEGF-A in the capillaries and reduced capillary density, which correlated inversely with blood levels of IS and Kyn and AHR activity in ECs. An AHR inhibitor treatment normalized postischemic angiogenic response in CKD mice to a non-CKD level. In a prospective cohort of PAD patients, plasma levels of tryptophan metabolites and plasma’s AHR-inducing activity in ECs significantly increased the risk of future adverse limb events. This work uncovers the tryptophan metabolite/AHR/β-catenin axis as a mediator of microvascular rarefaction in CKD patients and demonstrates its targetability for PAD in CKD models.     

Microbiota links to neural dynamics supporting threat processing

There is growing recognition that the composition of the gut microbiota influences behaviour, including responses to threat. The cognitive‐interoceptive appraisal of threat‐related stimuli relies on dynamic neural computations between the anterior insular (AIC) and the dorsal anterior cingulate (dACC) cortices. If, to what extent, and how microbial consortia influence the activity of this cortical threat processing circuitry is unclear. We addressed this question by combining a threat processing task, neuroimaging, 16S rRNA profiling and computational modelling in healthy participants. Results showed interactions between high‐level ecological indices with threat‐related AIC‐dACC neural dynamics. At finer taxonomic resolutions, the abundance of Ruminococcus was differentially linked to connectivity between, and activity within the AIC and dACC during threat updating. Functional inference analysis provides a strong rationale to motivate future investigations of microbiota‐derived metabolites in the observed relationship with threat‐related brain processes.     

Systemic lupus erythematosus‐related acute pancreatitis: An exceptional form with severe exocrine and endocrine pancreatitic failure in a Tunisian child

Acute pancreatitis may be the first manifestation in systemic lupus erythematosus or occur during evolution. It is a rare complication, which is often associated with other visceral manifestations. Outcome is usually favorable but can be serious. We report a case of a 17‐year‐old girl with a past history of systemic lupus erythematosus who developed acute pancreatitis revealed by abdominal pain. Elevated serum amylase and lipase levels and pancreatic enlargement on tomography confirmed the diagnosis. Although high‐dose corticosteroid was prescribed, the patient died from a refractory diabetic ketoacidosis.     

中国玫瑰痤疮临床特征分析和诊断标准再探讨

【摘要】 目的 在分析玫瑰痤疮临床特征的基础上,提出中国玫瑰痤疮诊断标准并验证其敏感性和特异性。方法 纳入2017年12月至2018年7月于中南大学湘雅医院皮肤科门诊初诊的3 350例玫瑰痤疮患者,分析患者表型及临床特征,提出改良版中国玫瑰痤疮诊断标准。全国28个中心对该标准进行临床验证,纳入2 269例玫瑰痤疮和2 408例其他面部皮肤病患者,与2017版美国国家玫瑰痤疮专家委员会（NRSEC）制订的国际诊断标准比较,评估其敏感性和特异性。结果 3 350例玫瑰痤疮患者均存在面中部持续性红斑（100%）。在1 861例主要表现为面颊部红斑的患者中,1 850例（99.4%）在红斑之前或同时出现阵发性潮红;在1 489例主要表现为鼻或口周部红斑的患者中,仅52例（3.5%）发生阵发性潮红; 342例有肥大增生的患者均在肥大增生改变之前发生持续性红斑。基于以上临床特征提出,面颊部可周期性加重的伴有阵发性潮红的持续性红斑,可诊断为玫瑰痤疮;对于表现为鼻、口周部持续性红斑的患者,需合并至少1项选择性表型（阵发性潮红、毛细血管扩张、丘疹脓疱、肥大增生改变或眼部症状）才可诊断为玫瑰痤疮。全国多中心临床验证结果显示,改良版中国玫瑰痤疮诊断标准敏感性为99.6%,接近国际标准100%,特异性为91.9%,而国际标准为73.3%。结论 改良版中国玫瑰痤疮诊断标准具有良好的敏感性和特异性,也更有利于增生肥大型玫瑰痤疮的早期诊断。