(+)-Catharanthine potentiates the GABA receptor by binding to a transmembrane site at the β(+)/α(-) interface near the TM2-TM3 loop.

(+)-Catharanthine, a coronaridine congener, potentiates the γ-aminobutyric acid type A receptor (GABAR) and induces sedation through a non-benzodiazepine mechanism, but the specific site of action and intrinsic mechanism have not beendefined. Here, we describe GABAR subtype selectivity and location of the putative binding site for (+)-catharanthine using electrophysiological, site-directed mutagenesis, functional competition, and molecular docking experiments. Electrophysiological and in silico experiments showed that (+)-catharanthine potentiates the responses to low, subsaturating GABA at β2/3-containing GABARs 2.

Health disparities, COVID-19, and maternal and childbirth outcomes: a meta-epidemiological study of equity reporting in systematic reviews.

Background: Pregnant women with COVID-19 are at increased risk for adverse maternal and pregnancy outcomes, and birth complications. Given the health outcome disparities among pregnant women of racial and ethnic minorities and the reliance of medical practice on systematic reviews and meta-analyses (SRMAs)-as they are the apical component in the hierarchy of evidence in medical research-the primary objective of the study is to examine the inclusion of the equity reporting in SRMAs focused on pregnancy outcomes and COVID-19 using PROGRESS-Plus equity framework. PROGRESS represents equity measures of Place, Race, Occupation, Gender, Religion, Education, Social capital, and Socio-economic status.

Upper airway hematoma: An unusual presentation of acute upper airway obstruction.

Acute upper airway obstruction secondary to supraglottic hematoma is a rare but life-threatening complication of oral anticoagulants, particularly with warfarin. Symptoms include sore throat, dysphagia, odynophagia, dysphonia, neck swelling, and dyspnea. We are reporting a case of an elderly male on warfarin therapy who developed acute upper airway obstruction due to spontaneous supraglottic hemorrhage.

Upper airway hematoma: An unusual presentation of acute upper airway obstruction.

Acute upper airway obstruction secondary to supraglottic hematoma is a rare but life-threatening complication of oral anticoagulants, particularly with warfarin. Symptoms include sore throat, dysphagia, odynophagia, dysphonia, neck swelling, and dyspnea. We are reporting a case of an elderly male on warfarin therapy who developed acute upper airway obstruction due to spontaneous supraglottic hemorrhage.

Cancer Screening Among Current and Former U.S. Military Personnel Compared to Civilians: A Cross-Sectional Analysis of the Behavioral Risk Factor Surveillance System.

Introduction: Approximately 3% of invasive U.S. cancer diagnoses are made among veterans in a Veterans Affairs (VA) clinic each year, while VA patients only comprise about 1.

(E)-3-furan-2-yl-N-phenylacrylamide (PAM-4) decreases nociception and emotional manifestations of neuropathic pain in mice by α7 nicotinic acetylcholine receptor potentiation.

Clinical intervention of pain is often accompanied by changes in affective behaviors, so both assays of affective and sensorial aspects of nociception play an important role in the development of novel analgesics. Although positive allosteric modulation (PAM) of α7 nicotinic acetylcholine receptors (nAChRs) has been recognized as a novel approach for the relief of sensorial aspects of pain, their effects on affective components of pain remain unclear. Therefore, we investigated whether PAM-4, a highly selective α7-nAChR PAM, attenuates inflammatory and neuropathic pain, as well as the concomitant depressive/anxiety comorbidities.

Type I and type II positive allosteric modulators of α7 nicotinic acetylcholine receptors induce antidepressant-like activity in mice by a mechanism involving receptor potentiation but not neurotransmitter reuptake inhibition. Correlation with mTOR intracellular pathway activation.

The aim of this study is to determine whether type I and type II positive allosteric modulators (PAMs) of α7 nicotinic acetylcholine receptors (nAChRs) induce antidepressant-like activity in mice after acute, subchronic, and chronic treatments, and to assess whether α7-PAMs inhibit neurotransmitter transporters and activate mTOR (mammalian target of rapamycin) and/or ERK (extracellular signal-regulated protein kinases) signaling. The forced swim (FST) and tail suspension (TST) test results indicated that NS-1738 (type I PAM), PNU-120596 and PAM-2 (type II PAMs) induce antidepressant-like activity after subchronic treatment, whereas PAM-2 was also active after chronic treatment. Methyllycaconitine (α7-antagonist) inhibited the observed effects, highlighting the involvement of α7 nAChRs in this process.

Clostridioides difficile spores stimulate inflammatory cytokine responses and induce cytotoxicity in macrophages.

Clostridioides difficile is a gram-positive, spore-forming anaerobic bacterium, and the leading cause of antibiotic-associated diarrhea worldwide. During C. difficile infection, spores germinate in the presence of bile acids into vegetative cells that subsequently colonize the large intestine and produce toxins.

Is the Antidepressant Activity of Selective Serotonin Reuptake Inhibitors Mediated by Nicotinic Acetylcholine Receptors?

It is generally assumed that selective serotonin reuptake inhibitors (SSRIs) induce antidepressant activity by inhibiting serotonin (5-HT) reuptake transporters, thus elevating synaptic 5-HT levels and, finally, ameliorates depression symptoms. New evidence indicates that SSRIs may also modulate other neurotransmitter systems by inhibiting neuronal nicotinic acetylcholine receptors (nAChRs), which are recognized as important in mood regulation. There is a clear and strong association between major depression and smoking, where depressed patients smoke twice as much as the normal population.

Using Google Trends and Twitter for Prostate Cancer Awareness: A Comparative Analysis of Prostate Cancer Awareness Month and Breast Cancer Awareness Month.

Background We evaluated (1) whether the public interest in prostate cancer and prostate cancer screening increased following Prostate Cancer Awareness Month (PCAM) and (2) whether PCAM was as effective as Breast Cancer Awareness Month (BCAM) at generating public interest. Methods  Using Google Trends, we measured search volume in PCAM and BCAM. We used the search volume in Google Trends as a proxy for changes in public interest from January 01, 2009 to December 31, 2018 worldwide, including the specific keywords: "Prostate Cancer"; "Prostate-Specific Antigen"; "Prostate Cancer Screening"; "Prostate Cancer Management"; "Breast Cancer"; "Breast Cancer Screening"; "Mammography"; and "Breast Cancer Management".

Recognition and Treatment of Tardive Dyskinesia in Individuals with Intellectual Disability.

Individuals with intellectual disability (ID) commonly suffer from comorbid psychiatric and behavioral disorders that are frequently treated by antipsychotic medications. All individuals exposed to first- and second/third- generation antipsychotics are at risk for developing tardive dyskinesia (TD), characterized by abnormal, involuntary movements of the mouth/tongue/jaw, trunk, and extremities. TD can be highly disruptive for affected individuals and their caregivers, causing embarrassment, isolation, behavioral disturbances, and reduced functioning and quality of life.

Acitretin induced lung injury by differentiation syndrome.

Differentiation syndrome is a life-threatening complication observed when retinoic acid is given to patients with acute promyelocytic leukemia. Retinoid compounds are also used in non-malignant conditions like psoriasis and it is rare to see differentiation syndrome in such settings. This reports details the clinical presentation and successful management of a patient with psoriasis who developed differentiation syndrome while on treatment with acitretin.

Correction to: Desformylflustrabromine, a positive allosteric modulator of α4β2-containing nicotinic acetylcholine receptors, enhances cognition in rats.

The original article can be found online.

Coronaridine congeners decrease neuropathic pain in mice and inhibit α9α10 nicotinic acetylcholine receptors and Ca2.2 channels.

The primary aim of this study was to determine the anti-neuropathic activity of (±)-18-methoxycoronaridine [(±)-18-MC] and (+)-catharanthine in mice by using the oxaliplatin-induced neuropathic pain paradigm and cold plate test. The results showed that both coronaridine congeners induce anti-neuropathic pain activity at a dose of 72 mg/kg (per os), whereas a lower dose (36 mg/kg) of (+)-catharanthine decreased the progress of oxaliplatin-induced neuropathic pain. To determine the underlying molecular mechanism, electrophysiological recordings were performed on α9α10, α3β4, and α4β2 nAChRs as well as voltage-gated calcium (Ca2.

Desformylflustrabromine, a positive allosteric modulator of α4β2-containing nicotinic acetylcholine receptors, enhances cognition in rats.

Rationale: The α4β2 nicotinic acetylcholine receptors (α4β2-nAChRs) may represent useful targets for cognitive improvement. It has been recently proposed that a strategy based on positive allosteric modulation of α4β2-nAChRs reveals several advantages over the direct agonist approach. Nevertheless, the procognitive effects of α4β2-nAChR positive allosteric modulators (PAMs) have not been extensively characterized.

Coronaridine congeners potentiate GABA receptors and induce sedative activity in mice in a benzodiazepine-insensitive manner.

To determine whether (+)-catharanthine induces sedative- or anxiolytic/anxiogenic-like activity in male mice, proper animal paradigms were used. The results showed that (+)-catharanthine induces sedative-like activity in the 63-72 mg/Kg dose range in a flumazenil-insensitive manner, but neither this effect nor anxiolytic/anxiogenic-like activity was observed at lower doses. To determine the underlying molecular mechanism of the sedative-like activity, electrophysiological and radioligand binding experiments were performed with (+)-catharanthine and (±)-18-methoxycoronaridine [(±)-18-MC] on GABA (GABARs) and glycine receptors (GlyRs).

Case Series: Redefining Severe Grade 5 Vaginismus.

Introduction: Vaginismus is poorly understood and relatively unknown among health care providers. For those who understand and treat vaginismus, few make an assessment of the severity of this condition. The importance of classifying the severity of vaginismus impacts the clinician's ability to diagnose and treat vaginismus, and understanding of the patient's experience.

Rapid Fire: Superior Vena Cava Syndrome.

Superior vena cava syndrome occurs from obstruction of the superior vena cava. The most common cause is malignancy. Small cell lung cancer and non-Hodgkin lymphoma are the most frequent culprits.

Is publication bias present in gastroenterological research? An analysis of abstracts presented at an annual congress.

Background: Publication bias is the tendency of investigators, reviewers, and editors to submit or accept manuscripts for publication based on their direction or strength of findings. In this study, we investigated if publication bias was present in gastroenterological research by evaluating abstracts at Americas Hepato-Pancreato-Biliary Congresses from 2011 to 2013.

Methods: We searched Google, Google Scholar, and PubMed to locate the published reports of research described in these abstracts.

Microplate fluorescence protease assays test the inhibition of select North American snake venoms' activities with an anti-proteinase library.

Snake envenomation is a relatively neglected significant world health problem, designated an orphan disease by the WHO. While often effective, antivenins are insufficient. Could another approach greatly aid inhibition of the venom toxins? New fluorescent substrates for measuring protease activity in microplate assays suitable for high throughput screening were tested and found reproducible with snake venom.