Not all that glitters is COVID-19: a case series demonstrating the need for histopathology when skin findings accompany SARS-CoV-2 infection.

BACKGROUND: Descriptions of cutaneous findings associated with COVID-19 have not been consistently accompanied by histopathology or confirmatory testing for SARS-CoV-2. OBJECTIVE: To describe and classify the cutaneous findings with supporting histopathology of confirmed COVID-19 inpatients. METHODS: We included consecutive inpatients with a confirmed diagnosis of COVID-19 for whom a dermatology consult was requested. A skin biopsy was performed in all cases. Skin findings were classified as being compatible with a cutaneous manifestation of COVID-19 or as representing a distinct clinical entity. RESULTS: Twenty-eight patients were studied in whom thirty-one dermatologic diagnoses were made. Twenty-two of the dermatoses were compatible with a cutaneous manifestation of COVID-19; nine entities were not associated with infection by SARS-CoV-2. The most common COVID-19-associated pattern was an exanthematous presentation. In four patients, a new pattern was observed, characterized by discrete papules with varied histopathological findings including a case of neutrophilic eccrine hidradenitis. No cases of pernio-like lesions were identified. Skin findings not associated with COVID-19 represented 29% of diagnoses and included Malassezia folliculitis, tinea, miliaria and contact dermatitis. LIMITATIONS: There is no gold-standard test to distinguish between viral exanthems and drug reactions. CONCLUSION: A histopathological study is critical before attributing skin findings to a manifestation of COVID-19.

The lupus patient traveller: a guide to the rheumatologist.

With an increasing number of international journeys occurring daily, there is also an increase in the need for appropriate medical advice for patients who will undertake such travel. In this context, the lupus patient presents a great challenge to the rheumatologist. However, the demand for such information by patients is low, and it has proven difficult for the medical community to adequately provide it. In this article, we carried out a literature review of the medical recommendations made for the lupus patient in order to guide the rheumatologist through the topic of travel medicine.

Optimization of culture conditions and bench-scale production of anticancer enzyme L-asparaginase by submerged fermentation from Aspergillus terreus CCT 7693.

L-Asparaginase amidohydrolase (EC 3.5.1.1) has received significant attention owing to its clinical use in acute lymphoblastic leukemia treatment and non-clinical applications in the food industry to reduce acrylamide (toxic compound) formation during the frying of starchy foods. In this study, a sequential optimization strategy was used to determine the best culture conditions for L-asparaginase production from filamentous fungus Aspergillus terreus CCT 7693 by submerged fermentation. The cultural conditions were studied using a 3-level, central composite design of response surface methodology, and biomass and enzyme production were optimized separately. The highest amount of biomass (22.0 g·L-1) was obtained with modified Czapek-Dox medium containing glucose (14 g·L-1), L-proline (10 g·L-1), and ammonium nitrate (2 g·L-1) fermented at 37.2 °C and pH 8.56; for maximum enzyme production (13.50 U·g-1), the best condition was modified Czapek-Dox medium containing glucose (2 g·L-1), L-proline (10 g·L-1), and inoculum concentration of 4.8 × 108 espore·mL-1 adjusted to pH 9.49 at 34.6 °C. The L-asparaginase production profile was studied in a 7 L bench-scale bioreactor and a final specific activity of 13.81 U·g-1 was achieved, which represents an increase of 200% in relation to the initial non-optimized conditions.

GSTT1 and GSTM1 null genotypes and the risk of gastric cancer: a case-control study in a Chinese population.

Glutathione S-transferase (GST) enzymes are involved in detoxification of many potentially carcinogenic compounds. The homozygous deletions or null genotypes of GSTT1 (theta class) and GSTM1 (mu class) genes may be associated with an increased risk of cancer. Few studies have evaluated the relationship between GSTT1, GSTM1 and the risk of gastric cancer, as well as the potential interactions between these genetic markers and other risk factors of gastric cancer in the Chinese population. We conducted a case-control study with 143 cases with gastric cancer, 166 chronic gastritis (CG) cases and 433 cancer-free population controls from Yangzhong County, China. The epidemiological data were collected by a standard questionnaire for all of the subjects, and blood samples were obtained from 91 gastric cancer cases, 146 CG cases, and 429 controls. GSTT1 and GSTM1 genotypes were assayed by the PCR method, and Helicobacter pylori infection was measured by the ELISA method. Using logistic regression model in SAS, we assessed the independent effects of GSTT1 and GSTM1 null genotypes on the risk of gastric cancer and their potential interactions with other factors. The prevalence of GSTM1 null genotype was 48% in gastric cancer cases, 60% in CG patients, and 51% in controls. The prevalence of GSTT1 null genotype was 54% in gastric cancer cases, 48% in CG patients, and 46% in controls. After controlling for age, gender, education, pack-years of smoking, alcohol drinking, body mass index, H. pylori infection, and fruit and salt intake, the adjusted odds ratio (OR) for GSTT1 and gastric cancer was 2.50 (95% confidence interval (CI), 1.01-6.22). When gastric cancer cases were compared with CG patients, the adjusted OR for GSTT1 was 2.33 (95% CI, 0.75-7.25). However, GSTT1 null genotype was not associated with the risk of CG when using population controls. No obvious association was found between GSTM1 and the risk of both gastric cancer and CG. Our results suggest that GSTT1 null genotype may be associated with an increased risk of gastric cancer in a Chinese population.

Effects of [3H]-BIDN, a novel bicyclic dinitrile radioligand for GABA-gated chloride channels of insects and vertebrates.

1. The radiolabelled bicyclic dinitrile, [3H]-3,3-bis-trifluoromethyl-bicyclo[2.2.1]heptane-2,2-dicarbonitrile ([3H]-BIDN), exhibited, specific binding of high affinity to membranes of the southern corn rootworm (Diabrotica undecimpunctata howardi) and other insects. A variety of gamma-aminobutyric acid (GABA) receptor convulsants, including the insecticides heptachlor (IC50, 35 +/- 3 nM) and dieldrin (IC50, 93 +/- 7 nM), displaced [3H]-BIDN from rootworm membranes. When tested at 100 microM, 1-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2.2.2]oct ane(EBOB), 4-t-butyl-2,6,7-trioxa-1-phosphabicy-clo[2.2.2]octane-1-thio ne (TBPS), 1-phenyl-4-t-butyl-2,6,7-trioxabicyclo[2.2.2]octane (TBOB) and picrotoxin failed to displace 50% of [3H]-BIDN binding to rootworm membranes indicating that the bicyclic dinitrile radioligand probes a site distinct from those identified by other convulsant radioligands. 2. Dissociation studies showed that dieldrin, ketoendrin, toxaphene, heptachlor epoxide and alpha and beta endosulphan displace bound [3H]-BIDN from rootworm membranes by a competitive mechanism. 3. Rat brain membranes were also shown to possess a population of saturable, specific [3H]-BIDN binding sites, though of lower affinity than in rootworm and with a different pharmacological profile. Of the insecticidal GABAergic convulsants that displaced [3H]-BIDN from rootworm, cockroach (Periplaneta americana) and rat brain membranes, many were more effective in rootworm. 4. Functional GABA-gated chloride channels of rootworm nervous system and of cockroach nerve and muscle were blocked by BIDN, whereas cockroach neuronal GABA(B) receptors were unaffected. 5. Expression in Xenopus oocytes of either rat brain mRNA, or cDNA-derived RNA encoding a GABA receptor subunit (Rdl) that is expressed widely in the nervous system of Drosophila melanogaster resulted in functional, homo-oligomeric GABA receptors that were blocked by BIDN. Thus, BIDN probes a novel site on GABA-gated Cl- channels to which a number of insecticidally-active molecules bind.

Spatiotemporal calcium signaling in a Drosophila melanogaster cell line stably expressing a Drosophila muscarinic acetylcholine receptor.

A muscarinic acetylcholine receptor (mAChR), DM1, expressed in the nervous system of Drosophila melanogaster, has been stably expressed in a Drosophila S2 cell line (S2-DM1) and used to investigate spatiotemporal calcium changes following agonist activation. Carbamylcholine (CCh) and oxotremorine are potent agonists, whereas application of the vertebrate M1 mAChR agonist, McN-A-343, results in a weak response. Activation of S2-DM1 receptors using CCh resulted in an increase in intracellular calcium ([Ca(2+)](i)) that was biphasic. Two distinct calcium sources were found to contribute to calcium signaling: (1) internal stores that are sensitive to both thapsigargin and 2-aminoethoxydiphenyl borate and (2) capacitative calcium entry. Spatiotemporal imaging of individual S2-DM1 cells showed that the CCh-induced [Ca(2+)](i) transient resulted from a homogeneous calcium increase throughout the cell, indicative of calcium release from internal stores. In contrast, ionomycin induced the formation of a "calcium ring" at the cell periphery, consistent with external calcium influx.

Polycyclic dinitriles: a novel class of potent GABAergic insecticides provides a new radioligand, [3H]BIDN.

The polycyclic dinitriles are a potent class of insecticides which are non-competitive GABA (gamma-aminobutyric acid) antagonists acting at the convulsant site. Comparison with other classes of GABA convulsant site ligands using molecular modelling has shown significant structural similarities. We have developed a pharmacophore model which unifies this class and some previous classes of GABA convulsants. Key pharmacophore elements are a polarizable functionality separated by a fixed distance from two H-bond accepting elements. This model is based on information from X-ray crystal structures and Sybyl using the Tripos force field. Using this pharmacophore model, numerous structural modifications were explored to enhance understanding of structure-activity relationships at the GABA receptor convulsant site of insects and mammals. A radiolabelled bicyclic dinitrile, [3H]BIDN [3H]3,3-bis-trifluoromethyl-bicyclo[2,2,1]heptane-2,2-dicarbonitrile+ ++), was prepared from this area of chemistry and was used as a probe for the interaction of polycyclic dinitriles at the target site.

A process model for competency-based education.

This article describes a process model for design and development of curricula. The model is based on learning theories of competency-based education. It is suggested that curricula so designed will, in conjunction with accreditation and credntialing, provide an additional mechanism for ensuring quality in professional practice.

Alteraciones del sueño en el enfermo grave. Un evento de gran repercusión y poco tomado en cuenta / Sleep disorders in the critically ill patient. An event of great impact and little taken into account

Resumen: El sueño favorece una mejor evolución y recuperación en los enfermos graves. Las alteraciones del sueño afectan con frecuencia a los enfermos internados en la unidad de terapia intensiva, su causa es multifactorial y se asocia con alteraciones del sistema inmunitario, disfunción en el anabolismo, retardo en los procesos regenerativos, desorganización neurofisiológica, disfunción cognitiva, delirio, incremento en los días de hospitalización y mortalidad. Las alteraciones del sueño en el paciente grave se caracterizan por anomalías del ritmo circadiano sueño-vigilia, índice elevado de despertares, fragmentación, reducción del sueño de ondas lentas y disfunción grave de la fase de movimientos oculares rápidos. Las intervenciones para su tratamiento son no farmacológicas y farmacológicas. De las farmacológicas la melatonina es un agente terapéutico promisorio para la profilaxis y para el tratamiento. El objetivo de este trabajo es revisar los conceptos actuales relacionados con la disfunción del sueño en el enfermo grave, su repercusión en la práctica clínica y las medidas a implementar para su profilaxis y tratamiento.

Abstract: Sleep is important for good outcome and recovery in critically ill patients. Sleep disturbances affect commonly critically ill patients and are associated with impair of immune system, anabolic and regenerative processes, neurophysiologic organization, cognitive dysfunction, delirium, prolonged Intensive Care Unit stay and mortality. The critically ill present pathologic sleep patterns characterized by abnormal circadian rhythm, high arousal and awakening index, reduced slow wave sleep and rapid eye movement sleep. Melatonin is a promissory prophylactic or therapeutic agent in the management of sleep disturbances. The aim of this paper is to review current concepts related to sleep disturbances in the critically ill, their clinical impact, prevention and the new therapeutic alternatives.