Toward Rapid and Automated Immunoassays: Using a Localized Electrochemical pH Modulation Platform to Perform a Single-Step Immunoassay.

An electrochemical platform for generating and controlling a localized pH microenvironment on demand is proposed by employing a closed-loop control algorithm based on an iridium oxide pH sensor input. We use a combination of solution-borne quinones and galvanostatic excitation on a prepatterned indium tin oxide (ITO) working electrode to modulate pH within a very well confined, small volume of solution close to the electrode surface. We demonstrate that the rate of pH change can be controlled at up to 2 pH s-1 with an excellent repeatability (±0.004). The desired pH microenvironment can be stably maintained for longer than 2 h within ±0.0012 pH. As a high-impact application of the platform technology, we propose a single-step immunoassay and demonstrate its utility in measuring C-reactive protein (CRP), a critical inflammatory marker in various conditions such as myocardial infarction and even SARS-Cov-2. Utilizing pH modulation technology along with pH-sensitive fluorescence dye simplifies the immunoassay process into a single-step, where a mixture of all of the reagents is incubated only for 1 h without any washing steps or the need to change solution. This simplified immunoassay process minimizes the hands-on time of the end-user and thus decreases technician-driven errors. Moreover, the absence of complicated liquid-handling hardware makes it more suitable and attractive for an ultracompact platform to ultimately be used in a point-of-care diagnostic assay.

Optimised photodynamic diagnosis for transurethral resection of the bladder (TURB) in German clinical practice: results of the noninterventional study OPTIC III.

PURPOSE: White light cystoscopy (WLC) is the standard procedure for visualising non-muscle invasive bladder cancer (NMIBC). However, WLC can fail to detect all cancerous lesions, and outcomes with transurethral resection of the bladder differ between institutions, controlled trials, and possibly between trials and routine application. This noninterventional study assessed the benefit of hexaminolevulinate blue light cystoscopy (HALC; Hexvix®, Ipsen Pharma GmbH, Germany) plus WLC versus WLC alone in routine use. METHODS: From May 2013 to April 2014, 403 patients with suspected NMIBC were screened from 30 German centres to perform an unprecedented detailed assessment of the additional detection of cancer lesions with HALC versus WLC alone. RESULTS: Among the histological results for 929 biopsy samples, 94.3 % were obtained from suspected cancerous lesions under either WLC or HALC: 59.5 % were carcinoma tissue and 40.5 % were non-cancerous tissue. Of all cancer lesions, 62.2 % were staged as Ta, 20.1 % as T1, 9.3 % as T2, 7.3 % as carcinoma in situ (CIS), and 1.2 % were unknown. Additional cancer lesions (+6.8 %) and CIS lesions (+25 %, p < 0.0001) were detected by HALC plus WLC versus WLC alone. In 10.0 % of patients, ≥1 additional positive lesion was detected with HALC, and 2.2 % of NMIBC patients would have been missed with WLC alone. No adverse events were observed. CONCLUSIONS: The results of this study demonstrate that HALC significantly improves the detection of NMIBC versus WLC alone in routine clinical practice in Germany. While this benefit is statistically significant across all types of NMIBC, it seems most relevant in CIS.

Do patients with motor neuron disease suffer from disorders of taste or smell?

Olfactory or gustatory dysfunction has been described in patients with motor neuron disease. This disorder along with other degenerative diseases has been tentatively linked with the olfactory vector hypothesis according to which a toxic agent may enter the organism via the nasal mucosa. In our study we assessed 26 patients diagnosed as suffering from motor neuron disease at various stages and compared them with 26 matched controls using 'Sniffin' Sticks' for smell and taste strips for taste testing. The two groups did not differ with respect to either ability. The smell test correlated with age, but not with the duration of the disease. We concluded that neither olfaction nor gustation seem to be linked to or influenced by the disease, making the causation by a toxin entering the body via the nasal or oral route rather unlikely as well as a degenerative process encompassing sensory pathways.

Anaesthesia protocol evaluation of the videolaryngoscopy with the McGrath MAC and direct laryngoscopy for tracheal intubation in 1000 patients undergoing rapid sequence induction: the randomised multicentre LARA trial study protocol.

INTRODUCTION: Rapid sequence induction of anaesthesia is indicated in patients with an increased risk of pulmonary aspiration. The main objective of the technique is to reduce the critical time period between loss of airway protective reflexes and rapid inflation of the cuff of the endotracheal tube to minimise the chance of aspiration of gastric contents. The COVID-19 pandemic has reinforced the importance of first-pass intubation success to ensure patient and healthcare worker safety. The aim of this study is to compare the first-pass intubation success rate (FPS) using the videolaryngoscopy compared with conventional direct laryngoscopy in surgical patients with a high risk of pulmonary aspiration. METHODS AND ANALYSIS: The LARA trial is a multicentre, patient-blinded, randomised controlled trial. Consecutive patients requiring tracheal intubation are randomly allocated to either the McGrath MAC videolaryngoscope or direct laryngoscopy using the Macintosh laryngoscope. The expected rate of FPS is 92% in the McGrath group and 82% in the Macintosh group. Each group must include a total of 500 patients to achieve 90% power for detecting a difference at the 5% significance level. Successful intubation with the FPS is the primary endpoint. The secondary endpoints are the time to intubation, the number of intubation attempts, the necessity of airway management alternatives, the visualisation of the glottis using the Cormack and Lehane Score and the Percentage Of Glottic Opening Score and definite adverse events. ETHICS AND DISSEMINATION: The project is approved by the local ethics committee of the Medical Association of the Rhineland Palatine state (registration number: 2020-15502) and medical ethics committee of the University of Freiburg (registration number: 21-1303). The results of this study will be made available in form of manuscripts for publication and presentations at national and international meetings. TRIAL REGISTRATION: NCT04794764.

Electron-Transport Characteristics through Aluminum Oxide (100) and (012) in a Metal-Insulator-Metal Junction System: Density Functional Theory-Nonequilibrium Green Function Approach.

Al2O3 is commonly used in modern electronic devices because of its good mechanical properties and excellent electrical insulating property. Although fundamental understanding of the electron transport in Al2O3 is essential for its use in electronic device applications, a thorough investigation for the electron-transport mechanism has not been conducted on the structures of Al2O3, especially in nanometer-scale electronic device settings. In this work, electron transport via Al2O3 for two crystallographic facets, (100) and (012), in a metal-insulator-metal junction configuration is investigated using a density functional theory-based nonequilibrium Green function method. First, it is confirmed that the transmission function, T(E), decreases as a function of energy in (E - E F) < 0 regime, which is an intuitively expected trend. On the other hand, in the (E - E F) > 0 regime, Al2O3(100) and Al2O3(012) show their own characteristic behaviors of T(E), presenting that major peaks are shifted toward lower energy levels under a finite bias voltage. Second, the overall conductance decay rates under zero bias are similar regardless of the crystallographic orientation, so that the contact interface seemingly has only a minor contribution to the overall conductance. A noteworthy feature at the finite bias condition is that the electrical current drastically increases as a function of bias potential (>0.7 V) in Al2O3(012)-based junction compared with the Al2O3(100) counterpart. It is elucidated that such a difference is due to the well-developed eigenchannels for electron transport in the Al2O3(012)-based junction. Therefore, it is evidently demonstrated that at finite bias condition, the contact interface plays a key role in determining insulating properties of Al2O3-Pt junctions.

Failure of monotherapy in primary monosymptomatic enuresis: a combined desmopressin and propiverine treatment regimen improves efficacy outcomes.

OBJECTIVE: To evaluate, in a prospective study, the combination of the antimuscarinic propiverine and the antidiuretic hormone-agonist desmopressin in children and adolescents not responsive to previous monotherapy, as in primary monosymptomatic enuresis (PME), combined treatments are considered a second-line approach after the failure of monotherapy. PATIENTS AND METHODS: The study included 122 children and adolescents (mean age 10.8 years, range 5-21) with PME and so far unresponsive to single or multiple monotherapy. Propiverine (body weight <30 kg, 15 mg/day; >or=30 kg, 20 mg/day) and desmopressin (0.4 mg/night) were administered over 3 months, followed by successive structured withdrawal programmes for propiverine and desmopressin, depending on the amount of loss of urine at night before treatment. RESULTS: The re-evaluation of unresponsive patients, incorporating video-urodynamics, showed neurogenic detrusor overactivity, isolated detrusor sphincter dyssynergia and vesicorenal reflux in 12.3% (15/122) of patients, so far falsely treated as enuresis. In 107 of 122 patients the diagnosis of PME was confirmed. The primary efficacy outcome, continence at night, was achieved in 104 of 107 patients (97.2%). During the individual follow-up periods (3-12 months), 23 of 107 (21.5%) patients relapsed after withdrawal of both medications. Adverse events of moderate intensity were rare (3.7%). CONCLUSION: Re-evaluation of patients after monotherapy has failed is justified, because other entities can be discovered in patients so far treated unsuccessfully for enuresis. The combination of propiverine and desmopressin is highly effective in children with PME. Our results support the case for further optimizing the inaugurated treatment algorithm of PME for treatment duration, dose-titration and structured withdrawal programmes, thus possibly further decreasing relapse rates.

Evaluation of the Unified Wilson's Disease Rating Scale (UWDRS) in German patients with treated Wilson's disease.

Wilson's disease (WD) is an inherited autosomal-recessive disorder of copper metabolism characterized by a wide variety of neurological, hepatic, and psychiatric symptoms. The aim of the present study was the development and evaluation of a clinical rating scale, termed Unified Wilson's Disease Rating Scale (UWDRS), to assess the whole spectrum of clinical symptoms in WD. Altogether 107 patients (mean age 37.6 +/- 11.9 years; 46 male, 61 female) with treated WD participated in the study. Cronbach's alpha as a measure of the internal consistency for the entire scale was 0.92, whereas the intraclass correlation coefficient (ICC) was 0.98 (confidence interval (CI(95%)) 0.97-0.99), indicating an excellent interrater reliability as determined in 32 patients. Besides the total score was significantly correlated with the earning capacity of the patients as indicated by an estimated Spearman's rho approximately 0.54 (CI(95%) 0.40-0.69, P < 0.001). In summary, the UWDRS appears to be a promising tool to assess the disease severity in WD. Its usefulness in clinical research and drug trials should be further addressed.

Geriatric Basics for the Neurohospitalist.

Due to the increasing age of the population, neurohospitalists are more frequently caring for old and very old people. Fundamental definitions and topics related to geriatric medicine are therefore of particular importance. In this review, common issues encountered in geriatric patients hospitalized on the neurology service are discussed. Focus is put on the geriatric assessment, multiprofessional diagnostic and therapeutic procedures, geriatric syndromes, pharmacotherapy of the aged, delirium, pain, and palliative management as they are relevant for the neurohospitalist. In addition, ethical questions are addressed.

Neuro-Ophthalmology at the Bedside: A Clinical Guide.

Neuro-ophthalmological signs and symptoms are common in the emergency department but are a frequent source of diagnostic uncertainties. However, neuro-ophthalmological signs often allow a precise neuro-topographical localization of the clinical problem. A practical concept is presented how to perform a neuro-ophthalmological examination at the bedside and to interpret key findings under the aspect of emergency medicine with limited resources.

Laser scanning tomography measurement of the extent of papilledema in the follow-up examination of patients with idiopathic intracranial hypertension.

OBJECT: The authors evaluated the characteristics of patients with idiopathic intracranial hypertension (IIH), and compared laser scanning tomography (LST) measurements of papilledema with the clinical parameters and cerebrospinal fluid (CSF) opening pressures obtained. METHODS: Twenty-four patients were included in this study; these individuals included 21 women and three men with a mean age of 35.5 +/- 9.7 years and a mean body mass index (BMI) of 35.4 +/- 8.3 kg/m2. The authors conducted a prospective follow-up study over a period of 12 months through a series of four consultations with each patient. These patients had a mean time to treatment of 6.2 +/- 7.9 months and, at the time of diagnosis, suffered a mean of 2.8 +/- 1.3 symptoms each. Laser scanning tomography of the optic disc revealed a mean global rim volume of 1.693 +/- 1.662 mm3 and a mean height of 0.604 +/- 0.306 mm. The mean CSF opening pressure was 31.3 +/- 6.3 cm H2O. RESULTS: During the follow-up period, all patients improved significantly with regard to clinical parameters (p < 0.001), BMI reduction (p < 0.001), and reduction of visual field deficits (p = 0.007); visual acuity remained unchanged. In all patients at each successive consultation, the CSF opening pressure was lower than it had been at the previous consultation (p = 0.001). Laser scanning tomography measurements demonstrated a statistically significant reduction in both optic disc parameters over the follow-up period (global rim volume, p = 0.044; mean height, p = 0.019). The CSF opening pressure and the LST measurements correlated significantly with the number of symptoms (CSF opening pressure, p < 0.001; global rim volume, p = 0.001; mean height, p < 0.001). The mean area under the receiver operating characteristic curve in detecting the presence of clinical symptoms was 0.87 for CSF opening pressure, 0.7 for rim volume, and 0.81 for mean optic disc height. CONCLUSIONS: Laser scanning tomography measurements are useful for evaluating the degree of papilledema in patients with IIH and correspond well with clinical data and measurements of CSF opening pressure. If a diagnosis of IIH is established, LST measurements may replace repeated CSF opening pressure measurements in follow-up monitoring.

[Are anti-dementia drugs worthwhile?]. / Lohnen Antidementiva?

The efficacy of the acetylcholinesterase inhibitors donepezil, galantamine and rivastigmine for Alzheimer's disease is well-documented by a number of studies. In Germany, the three substances are approved for the treatment of mild to moderate Alzheimer's disease; the glutamate antagonist memantine is approved for the treatment of moderate to severe Alzheimer's disease. The health economical benefit of these medicines is disputed and ultimately depends on the health policy evaluation. However, from the medical perspective, every newly diagnosed case of Alzheimer's disease justifies a therapeutic attempt. In a given case, changing between the three approved acetylcholinesterase inhibitors or memantine may be indicated. Whether a combination of the substances has advantages is currently being tested.

The four medical theses of Samuel Hahnemann (1755-1843).

Samuel Hahnemann, the founder of homoeopathy, over a period of 33 years wrote four medical theses at three different universities. The first, in 1779 at the University of Erlangen, Franconia, dealt with agents that allegedly induce spasms, granting him a MD degree. The second two theses in 1784 dealt with obstetrical matters and were imposed upon him by the University of Wittenberg, Saxony, for becoming a medical officer, a position he apparently aspired to mostly for financial reasons. The fourth thesis in 1812 at the University of Leipzig, Saxony, his most elaborate dissertation on a toxic plant, white hellebore, served as a habilitation, allowing him to hold university lectures in order to disseminate his new ideas.

Taste disorders in acute stroke: a prospective observational study on taste disorders in 102 stroke patients.

BACKGROUND AND PURPOSE: The aim of the study was to assess whether and how frequently patients with acute first-ever stroke exhibit gustatory dysfunction. METHODS: We performed a 1-year prospective observational study. Gustatory function was assessed using the standardized "taste strips" test. In addition, we assessed olfactory function, swallowing, stroke location, comorbidities, and the patients' medication. RESULTS: A total of 102 consecutive patients were enrolled (45 female, 57 male; mean age, 63 years); 31 of them (30%) exhibited gustatory loss and 7 (6%) had lateralized impairment of taste function. Predictors of impaired taste function were male gender (P=0.003), high National Institutes of Health Stroke Scale (NIHSS) score at admission (P=0.009), coexisting swallowing dysfunction (P=0.026), and a stroke of partial anterior circulation subtype (PACS) (P=0.008). In particular, in hypogeusic patients the lesion was most frequently localized in the frontal lobe (P=0.009). Follow-up examinations in 14 patients indicated improvement of taste sensitivity. CONCLUSIONS: Taste disorders after stroke are frequent. A significant association was found for male gender, high NIHSS score, swallowing disorder, and PACS, particularly in the frontal lobe. Generally, taste disorders after stroke seem to have a good prognosis.

Does improved problem-based teaching influence students' knowledge at the end of their neurology elective? An observational study of 40 students.

BACKGROUND: Elective programs for medical students in the last year of their university training are poorly evaluated. The goal of this study was to determine the gain in theoretical and practical skills in a group of students during their elective in neurology. Students were trained by either conventional teaching methods or applying improved problem-based teaching. METHOD: A test of 78 multiple choice questions regarding both, theoretical and practical aspects of clinical neurology, was presented to 21 students (9 female, 12 male). This group of students (group A) was trained according to the conventional teaching method. A subsequent group of students (intervention group B; n = 19; 9 female; 10 male) was educated using a modified teaching method that consisted of more problem-based learning, gathering experience with neurosonological and neurophysiological principles and in intense bedside teaching. The test was performed at the beginning and end of their elective period. The percentage increase in the tests was taken as the primary endpoint. In addition, all students were asked about their degree of satisfaction with the elective in general. RESULTS: Students of both groups did not differ with regard to age, gender, number of semesters, score of last examination and score of the test at the beginning of the elective. However, students who participated in the problem-based teaching group (group B) performed significantly better in the test at the end of the elective (increase 16.3% +/- 15.5) than those who were trained according to the conventional teaching program (percentage increase 6.3% +/- 9.4; p = 0.017). Students of both groups were highly satisfied with the elective in general. CONCLUSION: More problem-based teaching including practical exercises and intense bed-side teaching significantly improved students' performance. Thus, adaptation of teaching covering these aspects should be encouraged and might improve the neurological knowledge and skills of the students.

Multiple brain abscesses caused by Fusobacterium nucleatum treated conservatively.

BACKGROUND: Multiple brain abscesses are serious neurological problems with high mortality and disabling morbidity. The frequency is rising as a result of AIDS and the increasing number of immunocompromised patients. CASE STUDY: A 59-year-old woman developed signs and symptoms of diffuse brain dysfunction including fever and neck stiffness. A brain CT scan demonstrated nine contrast-enhancing ring-shaped lesions. Analysis of the cerebrospinal fluid using PCR-technique revealed DNA of Fusobacterium nucleatum. Conservative treatment with antibiotics was successful. The patient recovered with only mild cognitive deficits. RESULTS: The experience of our patient and the review of the literature indicate that multiple brain abscesses due to Fusobacterium nucleatum are rare. The most probable source is oral infection. CONCLUSION: Multiple brain abscesses may be caused by Fusobacterium nucleatum. Cerebrospinal fluid analysis using PCR technique is helpful with diagnosis. Conservative management can be successful.

Electrocerebral silence with preserved but reduced cortical brain perfusion.

Isoelectric electroencephalogram in conformance with clinical findings is strongly suggestive of brain death. In clinical practice, isoelectric electroencephalogram in not-brain-dead patients is rarely seen. We report on a 53-year-old patient who suffered ischaemic encephalopathy after cardiopulmonary arrest. He had residual brainstem function with sufficient spontaneous breathing and evidence of cerebral blood flow on single photon emission computed tomography scan, but his electroencephalogram was isoelectric. He survived this condition for more than 7 weeks. This case demonstrates that isoelectric electroencephalogram can not be equated with brain death, and that in prognostic assessment both clinical findings and supportive technical methods are mandatory.

Ejaculation-preserving transurethral resection of prostate and bladder neck: short- and long-term results of a new innovative resection technique.

INTRODUCTION: Loss of antegrade ejaculation is a risk with conventional resection of the prostate (transurethral resection of the prostate [TURP]). The aim of this study was to determine the short- and long-term preservation of antegrade ejaculation and functional results with the novel ejaculation-preserving TURP (epTURP). PATIENTS AND METHODS: Prospective evaluation of 89 consecutive patients with bladder outlet obstructions aged 27 to 78 years, enrolled from June 2001 to January 2005. Endpoints were change in objective (uroflowmetry, postvoid residual [PVR]), and subjective (International Prostate Symptoms Score [IPSS], Life Quality Index [LQI]; International Index of Erectile Function-5 [IIEF-5+] with two additional questions) measures of function. All patients received follow-up examinations at 3 and ≥60 months. RESULTS: Overall, 87 and 63 patients were evaluated after 3 and 60 months, respectively. Antegrade ejaculation was preserved in 79 of 87 (90.8%) patients at 3 months. Significant improvements in maximum flow rate (+14.3 mL/s), micturition volume (+71.6 mL), and PVR (-59 mL; p≤0.002 for all) were observed at 3 months. Micturition symptoms, as measured by IPSS and LQI, were also significantly reduced (mean change of 18.3 and 2.9, respectively; p<0.001). Improvements were maintained at 60 months. No serious adverse events were reported. Eight (12.7%) patients received a second epTURP due to the development of bladder neck scar tissue during long-term follow-up. CONCLUSION: Antegrade ejaculation was preserved with the use of epTURP with excellent outcome. Observed symptomatic and functional outcomes were comparable with conventional TURP. The results from this study underline the necessity of reviewing the old concept of ejaculation physiology.