Antidepressant effects of nicotine in an animal model of depression

Epidemiological studies indicate a high incidence of cigarette smoking among depressed individuals. Moreover, individuals with a history of depression have a much harder time giving up smoking. It has been postulated that smoking may reflect an attempt at self-medication with nicotine by these individuals. Although some animal and human studies suggest that nicotine may act as an antidepressant, further verification of this hypothesis and involvement of nicotinic cholinergic system in depressive symptoms is required. Flinders Sensitive Line (FSL) rats have been proposed as an animal model of depression. These rats, selectively bred for their hyperresponsiveness to cholinergic stimulation, show an exaggerated immobility in the forced swim test compared to their control Flinders Resistant Line (FRL) rats. Acute or chronic (14 days) administration of nicotine (0.4 mg/kg SC) significantly improved the performance of the FSL but not the FRL rats in the swim test. The effects of nicotine on swim test were dissociable from its effects on locomotor activity. Moreover, the FSL rats had significantly higher [³H]cytisine binding (selective for the α₄β₂ nicotinic receptor subtype) but not [¹²⁵I]alpha-bungarotoxin binding (selective for the α₇ subtype) in the frontal cortex, striatum, midbrain and colliculi compared to FRL rats. These data strongly implicate the involvement of central nicotinic receptors in the depressive characteristics of the FSL rats, and suggest that nicotinic agonists may have therapeutic benefits in depressive disorders. Received: 9 June 1998/Final version: 6 August 1998     

Hepatitis E infection in adults with primary immunodeficiency with or without immunoglobulin replacement therapy

BackgroundIn a context of secondary immunodeficiency, hepatitis E virus (HEV) infection can be responsible for chronic liver disease.Materials and methodsWe investigated HEV infection in patients with primary immunodeficiency treated (or not) with immunoglobulin (Ig) replacement therapy (IgRT) in France, a country with a high seroprevalence of HEV. In a nationwide study of individuals with primary immunodeficiency, 533 patients (349 and 184 receiving IgRT or not, respectively) were tested for HEV RNA and anti-HEV antibodies. In addition, 23 batches of five different commercially available immunoglobulin preparations were screened for anti-HEV IgG.ResultsThree of the 533 patients displayed markers of a recent HEV infection (HEV RNA in one case, and anti-HEV IgG and IgM in two) but no evidence of chronic liver disease. The overall seroprevalence of HEV was 50% (266 out of 533), with values of 68% and 16% in patients receiving IgRT or not, respectively (p<0.001). Anti-HEV IgG were detected in all batches of immunoglobulin preparations, although the titer varied from 3 to 127 IU/g IgG. Seroconversion was observed in 15 of the 22 (68%) patients tested before and after IgRT.DiscussionNo cases of chronic HEV-related disease were detected among patients with primary immunodeficiency and hypogammaglobulinemia, whether they received IgRT or not. This confirms that patients with primary immunodeficiency have a low risk of chronic infection despite a seroprevalence close to that observed in the French general population and that IgRT, which confers a high HEV seroprevalence, might play a key role in protection against chronic infection.     

Outcomes of post-exposure vaccination by modified vaccinia Ankara to prevent mpox (formerly monkeypox): a retrospective observational study in Lyon,France, June to August 2022

Modified vaccinia virus Ankara vaccine (MVA-BN; Bavarian Nordic) is recommended to contacts of mpox cases up to 14 days post-exposure but the effectiveness of this strategy is unknown. Among 108 adults (≥ 18 years old) who received one dose of MVA-BN after exposure to mpox, 11 (10%) cases of breakthrough mpox were observed. Sexual exposure was associated with the risk of breakthrough mpox (p = 0.0179). Samples taken from vaccinated breakthrough mpox cases had similar rates of infectious virus isolation than unvaccinated mpox cases.     

Nucleic Acid Preservation Card Surveillance Is Effective for Monitoring Arbovirus Transmission on Crocodile Farms and Provides a One Health Benefit to Northern Australia

The Kunjin strain of West Nile virus (WNV_KUN) is a mosquito-transmitted flavivirus that can infect farmed saltwater crocodiles in Australia and cause skin lesions that devalue the hides of harvested animals. We implemented a surveillance system using honey-baited nucleic acid preservation cards to monitor WNV_KUN and another endemic flavivirus pathogen, Murray Valley encephalitis virus (MVEV), on crocodile farms in northern Australia. The traps were set between February 2018 and July 2020 on three crocodile farms in Darwin (Northern Territory) and one in Cairns (North Queensland) at fortnightly intervals with reduced trapping during the winter months. WNV_KUN RNA was detected on all three crocodile farms near Darwin, predominantly between March and May of each year. Two of the NT crocodile farms also yielded the detection of MVE viral RNA sporadically spread between April and November in 2018 and 2020. In contrast, no viral RNA was detected on crocodile farms in Cairns during the entire trapping period. The detection of WNV_KUN and MVEV transmission by FTA^TM cards on farms in the Northern Territory generally correlated with the detection of their transmission to sentinel chicken flocks in nearby localities around Darwin as part of a separate public health surveillance program. While no isolates of WNV_KUN or MVEV were obtained from mosquitoes collected on Darwin crocodile farms immediately following the FTA^TM card detections, we did isolate another flavivirus, Kokobera virus (KOKV), from Culex annulirostris mosquitoes. Our studies support the use of the FTA^TM card system as a sensitive and accurate method to monitor the transmission of WNV_KUN and other arboviruses on crocodile farms to enable the timely implementation of mosquito control measures. Our detection of MVEV transmission and isolation of KOKV from mosquitoes also warrants further investigation of their potential role in causing diseases in crocodiles and highlights a “One Health” issue concerning arbovirus transmission to crocodile farm workers. In this context, the introduction of FTA^TM cards onto crocodile farms appears to provide an additional surveillance tool to detect arbovirus transmission in the Darwin region, allowing for a more timely intervention of vector control by relevant authorities.     

Differing effects of prosaccades and antisaccades on postural stability

The goal of the study was to examine the effect of different types of eye movements on postural stability. Ten healthy young adults (25 ± 3 years) participated in the study. Postural control was measured by the TechnoConcept© platform and recorded in Standard Romberg and Tandem Romberg conditions while participants performed five oculomotor tasks: two fixation tasks (central fixation cross, without and with distractors), two prosaccade tasks toward peripheral targets displayed 4° to the left or to the right of the fixation cross (reactive saccades induced by a gap 0 ms paradigm and voluntary saccades induced by an overlap 600 ms paradigm) and one antisaccade task (voluntary saccade made in the opposite direction of the visual target). The surface, the length, and the mean speed of the center of pressure were analyzed. We found that saccadic eye movements improved postural stability with respect to the fixation tasks. Furthermore, antisaccades were found to decrease postural stability compared to prosaccades (reactive as well as voluntary saccades). This result is in line with the U-shaped nonlinear model described by Lacour et al. (Neurophysiol Clin 38:411–421, 2008), showing that a secondary task performed during a postural task could increase (prosaccade task) or decrease (antisacade task) postural stability depending on its complexity. We suggest that the different degree of attentional resources needed for performing prosaccade or antisaccade tasks are, most likely, responsible for the different effect on postural control.     

Acute effects and long-term outcome of pulmonary vein isolation in combination with electrogram-guided substrate ablation for persistent atrial fibrillation

Complex fractionated atrial electrographic (CFAE) catheter ablation is a new approach for the treatment of atrial fibrillation (AF). It is unclear if acute results of this approach correspond to long-term outcome. The purpose of this study was to prospectively assess acute and long-term successes of an ablation approach combining pulmonary vein isolation (PVI) and ablation of CFAE areas for treatment of persistent AF. PVI and ablation of CFAE areas were performed in 35 patients with persistent AF (30 men, 57+/-9 years of age). At the end of the ablation procedure AF had terminated in 23 of 35 patients (66%) by conversion to sinus rhythm (8 of 23 patients, 35%) or organization to atrial tachycardia (15 of 23 patients, 65%). AF persisted in 12 of 35 patients (34%). At the end of the follow-up period (19+/-12 months), sinus rhythm was present in 26 of 35 patients (74%), including 9 patients with a repeat procedure. This group of 26 patients consisted of 7 of 8 patients (88%) with acute sinus rhythm after the first ablation, 11 of 15 patients (73%) with organization, and 8 of 12 patients (66%) with ongoing AF (p=0.32). In conclusion, a combined approach of PVI and CFAE ablation in persistent AF leads to acute AF termination in 66% and long-term maintenance of sinus rhythm in 74% of cases. However, long-term outcome was not predictable by acute results of the ablation procedure.     

Early virological failure with a combination of tenofovir, didanosine and efavirenz

OBJECTIVE: To describe the occurrence of a high early virological failure (VF) rate and development of resistance mutations in antiretroviral-naive patients receiving tenofovir, didanosine and efavirenz. METHODS: HIV-infected antiretroviral-naive patients with viral load > or =30 000 copies/ml were enrolled in a pilot randomized trial of tenofovir/didanosine (250 mg)/ efavirenz with (arm A) or without (arm B) lopinavir/r for the first 12 weeks. As six cases of early VF (a drop of <2 log at month 3, or a rebound of >1 log from the nadir) were detected (five in arm B and one in arm A who had previously stopped lopinavir/r) an unplanned interim analysis was performed. RESULTS: A total of 29 out of 36 enrolled patients completed at least 3 months of follow-up and were included in the interim analysis. An intent-to-treat analysis showed treatment failure in 7/15 (46.7%) patients in arm B (five VF, one lost, one switched) versus 2/14 (14.3%) in arm A (one lost, one switched) (P=0.109). The patient in arm A who interrupted lopinavir/r at day 3 and continued with tenofovir/didanosine/efavirenz later developed VF. At baseline, 6/6 VF patients had VL >100000 copies/ml and an advanced stage of disease (CD4 <200 plus CDC stage C or B3) versus 0/8 non-VF patients taking the triple drug regimen (P<0.001). At failure, G190S/E alone or associated with K103N and K101R mutations was detected in five patients, and K103N/L1001/V108l in the sixth patient. Additionally, L74V/I and K65R were detected in four and two patients, respectively. CONCLUSIONS: A high early virological failure rate and the occurrence of resistance mutations were detected in a group of antiretroviral-naive patients treated with tenofovir/didanosine/efavirenz.     

Postoperative management of Dupuytren’s disease with topical nitroglycerin

Dupuytren’s contracture remains a significant clinical challenge due to associated complications and a recurrence rate of up to 60%. Commonly, the operated skin tends to rebuild scar in the area of surgery. Assuming local ischemia as an etiological factor, two cases in which topical nitroglycerin was used following surgical treatment of Dupuytren’s disease are presented. In these patients, no raised scar formation developed during healing. At least six months after surgery, disease recurrence was not noted and the patients and surgeon reported improved skin quality. In the present study, the use of topical nitroglycerin, a local vasodilator, appeared to prevent recurrent scar formation, possibly through prevention of local ischemia. Further study and follow-up is necessary.