Substrate Specificity of ABCB Transporters Predicted by Docking Simulations Can Be Confirmed by Experimental Tests.

ATP-binding cassette (ABC) transporters, particularly those of subfamily B, are involved in cell detoxification, multidrug resistance, drug treatment pharmacodynamics, and also ecological adaptation. In this regard, ABCB transporters may play a decisive role in the co-evolution between plants and herbivores. Cardenolides, toxic steroid glycosides, are secondary plant metabolites that defend plants against herbivores by targeting their sodium-potassium ATPase.

EUNOS 2023 Practical Neuro-Ophthalmology Course: Groningen, The Netherlands, June 1st-2nd, 2023.

The European Neuro-Ophthalmology Society (EUNOS) practical neuro-ophthalmology course, henceforth referred to as the EUNOS course, took place in 2023 in Groningen, the Netherlands. This two-day international event featured a blend of plenary lecture sessions, workshops, and case reports, providing a practical update on fundamental neuro-ophthalmology topics for residents and young specialists in both neurology and ophthalmology.

Data Driven Computational Design and Experimental Validation of Drugs for Accelerated Mitigation of Pandemic-like Scenarios.

Emerging pathogens are a historic threat to public health and economic stability. Current trial-and-error approaches to identify new therapeutics are often ineffective due to their inefficient exploration of the enormous small molecule design space. Here, we present a data-driven computational framework composed of hybrid evolutionary algorithms for evolving functional groups on existing drugs to improve their binding affinity toward the main protease (M) of SARS-CoV-2.

The utility of collateral student drinking reports: Evidence from a biomarker study.

Introduction: Researchers have increasingly used collateral informants to validate the reports provided by primary research subjects. We assessed the utility of collateral informants for college students in a study that incorporates biomarkers to validate student reports of recent drinking behavior.

Methods: Students from a Midwestern university were randomly selected for a study in which they provided 90-day Timeline Followback data, hair and fingernail specimens for ethylglucuronide (EtG) testing, and information about collateral (friends or peers) informants who were familiar with their drinking behavior.

Detection of codeine, morphine, 6-monoacetylmorphine, and meconin in human umbilical cord tissue: method validation and evidence of in utero heroin exposure.

Background: Heroin abuse is a significant public health issue and is on the rise because of the unintended consequences of strengthening controls for nonmedical use of prescription pain killers. Included in this trend is an increase in opiate exposed newborns that are particularly vulnerable to a number of negative health outcomes.

Methods: After presenting a fully validated liquid chromatography-tandem mass spectrometric method for codeine, morphine, 6-monoacetylmorphine, and meconin, a metabolite of the heroin contaminant noscapine, we compared the outcome of 46 authentic umbilical specimens with the results generated using a previous less sensitive method that did not include meconin.

Ethyl glucuronide in hair and fingernails as a long-term alcohol biomarker.

Aims: This study aimed to evaluate the performance of ethyl glucuronide (EtG) in hair and fingernails as a long-term alcohol biomarker.

Design: Cross-sectional survey with probability sampling.

Setting: Midwestern United States.

Liquid Chromatography-Tandem Mass Spectrometry Assay to Detect Ethyl Glucuronide in Human Fingernail: Comparison to Hair and Gender Differences.

Over the past decade, the use of hair specimens for the long-term detection of the alcohol biomarker ethyl glucuronide has been increasing in popularity and usage. We evaluated the usefulness of fingernail clippings as a suitable alternative to hair for ethyl glucuronide detection. A liquid chromatography-tandem mass spectrometry method for the detection of ethyl glucuronide in fingernail clippings was fully validated and used to analyze the hair and/or fingernail specimens of 606 college-aged study participants.

Thyrotropin-releasing hormone selectively stimulates human hair follicle pigmentation.

In amphibians, thyrotropin-releasing hormone (TRH) stimulates skin melanophores by inducing secretion of α-melanocyte-stimulating hormone in the pituitary gland. However, it is unknown whether this tripeptide neurohormone exerts any direct effects on pigment cells, namely, on human melanocytes, under physiological conditions. Therefore, we have investigated whether TRH stimulates pigment production in organ-cultured human hair follicles (HFs), the epithelium of which expresses both TRH and its receptor, and/or in full-thickness human skin in situ.

Determination of amphetamine and methamphetamine in umbilical cord using liquid chromatography-tandem mass spectrometry.

The use of meconium as a drug-screening matrix for newborns has been the gold standard of care for the past two decades. A recent study using matched pairs of meconium and umbilical cord demonstrated a high degree of agreement. The use of liquid chromatography-tandem mass spectrometry as a means to confirm amphetamines presumptive positive umbilical cord specimens for amphetamine and methamphetamine is described here for the first time.

Using umbilical cord tissue to detect fetal exposure to illicit drugs: a multicentered study in Utah and New Jersey.

Objective: We assessed umbilical cord tissue as a means of detecting fetal exposure to five classes of drugs of abuse.

Study Design: In a multicentered study in Utah and New Jersey, we collected umbilical cord tissue when high-risk criteria were met for maternal illicit drug use. The deidentified umbilical cord specimens were analyzed for five drug classes: methamphetamine, opiates, cocaine, cannabinoids and phencyclidine.

Testing for fetal exposure to illicit drugs using umbilical cord tissue vs meconium.

Objective: We assessed the agreement of testing for fetal exposure to illicit drugs contrasting paired specimens of meconium vs umbilical cord tissue.

Methods: We obtained paired samples of meconium and umbilical cord tissue from 118 pregnancies with high suspicion of illicit drug use by the mothers. Each specimen was tested for amphetamines, opiates, cocaine, cannabinoids, and phencyclidine using drug class-specific immunoassays.

Unusual EEG theta rhythms over central region in Rett syndrome: considerations of the underlying dysfunction.

In 10 female patients (age 2-26 years) with clinical evidence of Rett Syndrome (RS), unusual and prominent rhythmical theta activity (4-5/sec or 5-6/sec) proved to be the outstanding EEG feature. This pattern was present in waking state and/or sleep. When it was noted in the waking state, the localization (vertex, central region and vicinity) and blocking responses to active or passive movements suggested a slow equivalent of Rolandic mu rhythm (in two patients associated with a posterior 10-12/sec alpha rhythm).

Antiepileptic medication and oral contraceptive interactions: a national survey of neurologists and obstetricians.

Hepatic enzyme-inducing antiepileptic drugs (AEDs) lower oral contraceptive (OC) sex hormone levels approximately 40% and increase the risk of unplanned pregnancies in women with epilepsy. AEDs also increase the risk of birth defects in offspring of women with epilepsy. We performed a national survey to determine obstetricians' and neurologists' knowledge of OC and AED interactions and the risk of birth defects for women with epilepsy taking AEDs.

Cognitive effects of resecting basal temporal language areas.

Electrical stimulation of the basal temporal region of the dominant hemisphere before partial temporal lobectomy for epilepsy sometimes produces temporary interruption of language function, but the significance of removal of this area is unknown. We evaluated the correlation between resection of the basal temporal language areas (BTLA) and certain types of postoperative language deficits. In a population of 25 patients, we mapped the inferolateral temporal lobe with cortical electrical stimulation, verifying the positions of the stimulating electrodes with three-dimensional computed tomography (CT).

Sensitive and specific detection of the 4B5 antigen in bronchial lavage specimens from patients with primary bronchogenic carcinoma.

The monoclonal antibody 4B5 binds to a mucin-like antigen elaborated by respiratory epithelium of patients with non-small cell bronchogenic carcinoma. Several immunoassay formats were used to determine the presence of the antigen in lavage specimens. A qualitative immunodrop binding assay showed immunoreactivity in 37 (64%) of 58 specimens from patients with non-small cell lung cancer.

[Nursing care of the elderly. Moral and ethical problems].

The article deals with moral and ethical issues involved in nursing care of the elderly during their hospitalization. Nursing interventions resulted in iatrogenic complications as well as nursing dilemmas are also discussed.

Detection of a novel marker in the bronchial secretions of patients with non-small cell lung cancer using the 4B5 monoclonal antibody.

A murine monoclonal antibody designated 4B5 was raised against the high molecular weight fraction of pooled sputum from patients with non-small cell lung cancer (NSCLC). Immunohistochemical staining indicated that 4B5 binds to histologically normal bronchial epithelium distant from tumor in 72% (39 of 54) of patients with NSCLC, but it binds to the primary cancer in only 13% (7 of 54) of the same patients. The antibody reacted less intensely with the bronchial epithelium in 16.

Evidence for a protonmotive force related regulatory system in Escherichia coli and its effects on lactose transport.

Strains of Escherichia coli with mutations in the eup (energy-uncoupled phenotype) locus do not grow on nonfermentable carbon sources, have reduced growth yields on limiting glucose, are insensitive to colicins A and K, exhibit resistance to aminoglycoside antibiotics, and are defective in protonmotive force coupled active transport. eup mutations do not result in lowered protonmotive force. Here we show that deenergization of a eup+ strain results in the appearance of a new low KT, low Vmax form of the lactose carrier; in a strain deleted of the eup locus, deenergization does not evoke the low KT, low Vmax form of the lactose carrier.