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Double differential (angular and energy) neutron distributions were measured using an activation foil technique. Reactions were induced by impinging two low-energy heavy-ion beams accelerated with the GANIL CSS1 cyclotron: (36S (12 MeV/u) and 208Pb (6.25 MeV/u)) onto thick natCu targets. Results have been compared to Monte-Carlo calculations from two codes (PHITS and FLUKA) for the purpose of benchmarking radiation protection and shielding requirements. This comparison suggests a disagreement between calculations and experiment, particularly for high-energy neutrons.

Objective: A suicide audit was pilot implemented in order to generate recommendations on how to improve suicide prevention., Methods: Thirty-nine consecutive suicides that occurred in Montreal, Canada from January to October 2016 were audited. A retrospective analysis of their life trajectory and service utilization was conducted using the psychological autopsy method, which included interviewing suicide-bereaved survivors and examining health and social services records and the coroner's investigation file. A psychosocial and service utilization profile was drawn for each decedent. A multidisciplinary panel reviewed each case summary to identify gaps in terms of individual intervention, provincial public health and social services, and regional programs., Results: Five main suicide prevention recommendations were made to prevent similar suicides: (1) deploy mobile crisis intervention teams (short-term, high-intensity, home-based treatment) in hospital emergency departments; (2) train primary and specialized mental health care professionals to screen for and manage substance use disorders; and (3) implement public awareness campaigns to encourage help seeking for depression and substance use disorders; (4) access for all, regardless of age, to an effective psychosis treatment program; and (5) provide universal access to a general practitioner, especially for men., Conclusions: The suicide audit procedure was implemented effectively and targeted recommendations were generated to prevent similar suicides. However, resistance from medical and hospital quality boards arose during the process, though these could be allayed if regional and provincial authorities actively endorsed the multidisciplinary and multi stakeholders suicide audit process. HighlightsA bottom-up approach to generate recommendations for suicide prevention.Implementation was challenging with resistance to our interdisciplinary approach.The audit needs the support of the regional health department to lift barriers.

Background: Suicide is a major public health concern. In 2017, the suicide rate in Canada was 11 per 100,000 inhabitants. According to literature, 1 in 5 people have experienced a death by suicide during their lifetime. The aim of this study was to describe the met and unmet needs of suicide-bereaved survivors and to provide postvention recommendations., Methods: Further to an exploratory mixed-method audit of 39 suicides that occurred in Montreal (Canada) in 2016, suicide-bereaved survivors (n = 29) participated in semi-structured interviews and completed instruments to discuss and assess potential pathological grief, depression (PHQ-9), and anxiety (GAD-7), as well as health and social services utilization. A panel then reviewed each case and provided recommendations. The mean age of participants was 57.7 years and 23 were women., Results: Although help was offered initially, in most cases by a health professional or service provider (16/29), 22 survivors would have liked to be contacted by telephone in the first 2 months post suicide. Four categories of individual unmet needs (medical/pharmacological, information, support, and outreach) and one collective unmet need (suicide pre/postvention training and delivery) emerged., Conclusions: Although Quebec provincial services have been developed and offered to suicide-bereaved survivors in the past decade, many dwindled over time and none has been applied systematically. Recommendations for different stakeholders (Ministry of Health and Social Services, coroners, NGOs, and representatives of suicide-bereaved survivors) outlined in this study could be an interesting first step to help develop a suicide pre/postvention strategy.

Previously, a sub-population of defeated anesthetized rats (Dlow) was characterized by persistent low blood levels of brain-derived neurotrophic factor (BDNF) at day 29 and autonomic alteration at day 30 after social challenge, while the other population (Dhigh) was similar to non-defeated (ND) animals. The aims of this study were to determine the time-course of autonomic dysfunction in awake animals, and whether Dhigh and/or Dlow were vulnerable to cardiac events. Defeated animals were exposed to four daily episodes of social defeats from day 1 to day 4. At day 30, anesthetized Dlow displayed decreased experimental and spontaneous reflex responses reflecting lower parasympathetic efficiency. In addition, Dlow but not Dhigh were characterized by left ventricular hypertrophy at day 30. Telemetric recordings revealed that Dlow had increased low frequency-to-high frequency ratio (LF/HF) and diastolic (DBP) and systolic (SBP) blood pressure, associated with decreased HF and spontaneous baroreflex responses (BRS) from day 3 to day 29. LF/HF, DBP and SBP recovered at day 5, and HF and BRS recovered at day 15 in Dhigh. Ventricular premature beats (VPBs) occurred in Dlow and Dhigh animals from day 5. Time course of VBP fluctuations in Dhigh mirrored that of HF and BRS, but not that of LF/HF, DBP and SBP. These results suggest that a psychosocial stress associated to low serum BDNF levels can lead to vulnerability to persistent autonomic dysfunction, cardiac hypertrophy and ventricular ectopic beats. The parasympathetic recovery seen in Dhigh may provide protection against cardiac events in this population., (© 2020 The Authors. Published by Elsevier Inc.)

A high prevalence of intermediate cardiometabolic risk factors and obesity in chronic obstructive pulmonary disease (COPD) has suggested the existence of pathophysiological links between hypertriglyceridemia, insulin resistance, visceral adiposity, and hypoxia or impaired pulmonary function. However, whether COPD contributes independently to the development of these cardiometabolic risk factors remains unclear. Our objective was to compare ectopic fat and metabolic profiles among representative individuals with COPD and control subjects and to evaluate whether the presence of COPD alters the metabolic risk profile. Study participants were randomly selected from the general population and prospectively classified as non-COPD controls and COPD, according to the Global Initiative for Chronic Obstructive Lung Disease classification. The metabolic phenotype, which consisted of visceral adipose tissue area, metabolic markers including homeostasis model assessment of insulin resistance (HOMA-IR), and blood lipid profile, was obtained in 144 subjects with COPD and 119 non-COPD controls. The metabolic phenotype was similar in COPD and controls. The odds ratios for having pathologic values for HOMA-IR, lipids and visceral adipose tissue area were similar in individuals with COPD and control subjects in multivariate analyses that took into account age, sex, body mass index, tobacco status and current medications. In a population-based cohort, no difference was found in the metabolic phenotype, including visceral adipose tissue accumulation, between COPD and controls. Discrepancies between the present and previous studies as to whether or not COPD is a risk factor for metabolic abnormalities could be related to differences in COPD phenotype or disease severity of the study populations., Competing Interests: MM, CB, NA and VC have no conflicts of interest to declare. DV report grants from Astra Zeneca France outside the submitted work. MEP is research scholars from the Fonds de Recherche du Québec-Santé (FRQ-S) JPD reports personal fees from Abbott Laboratories, AstraZeneca, GSK, Merck and Pfizer Canada Inc. and personal fees from Abbott Laboratories, Sanofi and Torrent Pharmaceuticals Ltd. outside the submitted work. WCT reports grants from Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants-93326) with industry partners AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd, during the conduct of the study. JB reports grants from Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants-93326) with industry partners AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, NovartisPharma Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd, during the conduct of the study. JLP report grants from Air Liquide Foundation, Agiradom, AstraZeneca, Fisher and Paykel, Mutualia, Philips, Resmed and Vitalaire outside the submitted work and personnal fees from Agiradom, AstraZeneca, Boehringer Ingelheim, Jazz pharmaceutical, Night Balance, Philips, Resmed and Sefam outside the submitted work. FM reports grants and personal fees from Boehringer Ingelheim and GSK, grants from Nycomed and grants and personal fees from Novartis outside the submitted work. All fees are pooled with other revenues of the group of pulmonologists to which FM is a member and then shared among members of the group. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Exertional dyspnea is a cardinal feature of chronic obstructive pulmonary disease (COPD) and a major cause of activity limitation. Although dual bronchodilation is more effective than bronchodilator monotherapy at improving resting pulmonary function, it is unclear to which extent this translates into superior relief of exertional dyspnea., Methods: We conducted a randomized controlled, double-blind, cross-over trial comparing indacaterol 110 µg/glycopyrronium 50 µg once daily (OD) with tiotropium 50 µg OD in patients with moderate to severe COPD and resting hyperinflation (functional residual capacity >120% of predicted value). The primary outcome was Borg dyspnea score at the end of a 3-min constant speed shuttle test after 3 weeks of treatment. Secondary outcomes included changes in Borg dyspnea score after the first dose of study medication, expiratory flows and lung volumes. Statistical analysis was conducted using a cross-over analysis of variance model with repeated measurements., Results: A total of 50 patients with COPD and a mean forced expiratory volume in 1 s of 54 ± 11% (mean ± SEM) predicted participated in the cross-over phase of the trial. Compared with baseline, there was a decrease in dyspnea after the first dose of medication with indacaterol/glycopyrronium [mean -1.00, 95% confidence interval (CI) -1.49 to -0.52] but not with tiotropium alone (mean -0.36, 95% CI -0.81 to 0.08). The reduction in dyspnea after the first dose was statistically significant between the two treatments (mean difference of -0.64, 95% CI -1.11 to -0.17). Despite indacaterol/glycopyrronium providing further bronchodilation and lung deflation throughout the trial, the reduction in dyspnea was not sustained at 3 weeks of treatment (mean between-treatment difference at 3 weeks of 0.09, 95% CI -0.44 to 0.61)., Conclusion: In comparison with bronchodilator monotherapy, indacaterol/glycopyrronium provided greater immediate exertional dyspnea relief, although this difference was not sustained after 3 weeks of therapy despite evidence of further bronchodilation and lung deflation. The reviews of this paper are available via the supplemental material section.

After social stress, rats become vulnerable to depression, and this state is characterized by persistent low blood levels of brain-derived neurotrophic factor (BDNF). The aim of this study was to determine whether low BDNF levels are associated with long term autonomic changes. Defeated animals were subjected to four daily episodes of social defeats. Twenty five days later, defeated rats with low BDNF levels (Dlow) still displayed elevated sympathetic tone (as indicated by an elevated low frequency to high frequency ratio (LF/HF) in heart rate) and elevated blood pressure, as well as reduced baroreflex sensitivity (BRS). In contrast, those with higher BDNF levels (Dhigh) similar to controls, did not. Dlow animals persistent cardiovascular changes were abolished by acute inhibition of the dorsomedial nucleus of the hypothalamus (DMH). These cardiovascular changes were also prevented by chronic sub-cutaneous osmotic infusion of losartan, an angiotensin II type 1 receptor (AT 1 ) receptor antagonist, started immediately after social defeat. In conclusion, the results show that greater vulnerability to stress consequences following a traumatic event is associated with an elevated LF/HF ratio, a persistent high blood pressure and a low BRS, all due to an AT 1 receptor activation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The present study used a genetically informed design of twins raised in the same family (375 monozygotic and 290 dizygotic twins; 50.2% girls) to examine the association between adolescents' genetic risk for depressive symptoms and the course of the parent-child relationship quality throughout adolescence. Depressive symptoms and the quality of the parent-adolescent relationships were measured through adolescents' self-reports from ages 13 to 17. Group-based trajectory modeling revealed that most adolescents experienced high-quality relationships with both of their parents, characterized by high levels of warmth and low levels of conflict, and marked by gradual changes over adolescence. However, 3% of adolescents showed a trajectory of high and increasing conflict with their mothers and 16% of adolescents showed a trajectory of low warmth with their fathers, which decreased until mid-adolescence before increasing thereafter. Moreover, in line with an evocative gene-environment correlation process, a higher genetic vulnerability to depressive symptoms increased the likelihood of following a more problematic relationship trajectory with parents. This rGE was mediated by adolescents' actual depressive behavior symptoms. Results also suggest that adolescents' depression symptoms may affect girls' and boys' relationship with their parents in a similar way, with specific sex-patterns revolving more around the sex of the parent. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

This study examined the unique roles of support and conflict in the relationship with the mother and the father in predicting changes in adolescents' depressive symptoms over a 1-year period. Potential moderating effects of genetic factors (Gene × Environment interaction) and sex were also investigated. This study utilized a design of twins raised in the same family, based on a sample of 121 monozygotic and 88 dizygotic same-sex twin pairs (418 individuals; 52.2% girls) assessed in Grade 8 (M = 14.09, SD = .29) and in Grade 9 (M = 15.07, SD = .26). Depressive symptoms and the parent-adolescent relationship quality were measured with self-report questionnaires. Multilevel regressions revealed that a lack of support in the father-adolescent relationship predicted increased depressive symptoms among all adolescents, whereas conflict in the father-adolescent relationship predicted increased depressive symptoms more strongly as adolescents' genetic vulnerability for depressive symptoms increased. Moreover, a high level of support in the relationship with the mother predicted increased depressive symptoms in boys-but not girls-with a high genetic risk for such problems. In line with a diathesis-stress model of psychopathology, these findings suggest that relationship quality with both parents might impact girls' and boys' depressive symptoms but that these associations depend to some extent on adolescents' genetic vulnerabilities.

Recent studies have demonstrated that a mild stimulation of the dorsomedian nucleus of the hypothalamus (DMH), a defense area, induces the inhibition of the carotid chemoreflex tachypnea. DMH activation reduces the cardiac chemoreflex response via the dorsolateral part of the periaqueductal grey matter (dlPAG) and serotonin receptors (5-HT 3 subtype) in the nucleus tractus solitarius (NTS). The objectives of this study were to assess whether dlPAG and subsequent NTS 5-HT 3 receptors are involved in chemoreflex tachypnea inhibition during mild activation of the DMH. For this purpose, peripheral chemoreflex was activated with potassium cyanide (KCN, 40 μg/rat, i.v.) during electrical and chemical minimal supra-threshold (mild) stimulation of the dlPAG or DMH. In both situations, changes in respiratory frequency (RF) following KCN administration were reduced. Moreover, pharmacological blockade of the dlPAG prevented DMH-induced KCN tachypnea inhibition. Activation of NTS 5-HT 3 receptors also reduced chemoreflex tachypnea in a dose-dependent manner. In addition, blockade of NTS 5-HT 3 receptors with granisetron (2.5 but not 1.25 mM), or the use of mice lacking the 5-HT 3a receptor (5-HT 3a KO), prevented dlPAG-induced KCN reductions in RF. A respiratory hypothalamo-midbrain-medullary pathway (HMM) therefore plays a crucial role in the inhibition of the hyperventilatory response to carotid chemoreflex., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Recent observations from our group seem to indicate that repeated stress-evoked dorsomedian hypothalamic nucleus (DMH) activation in rats can lead to persistent bradypnea. One possibility was that respiratory responses to peripheral chemoreceptor activation were reduced by DMH stimulation. In the present study, we therefore investigated the effect of minimal supra-threshold DMH stimulation on respiratory carotid chemoreflex responses. For this purpose, the chemoreflex was activated by potassium cyanide (KCN, 40μg/rat, i.v.) during electrical and chemical stimulation of the DMH. In both situations, changes in breathing frequency but not tidal volume responses to KCN administration were reduced. These findings suggest that low DMH neurotransmission negatively affects respiratory chemoreflex responses and may be involved in stress-induced bradypnea., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background and Purpose: It has recently been suggested that 5-HT 3 receptor blockade enhances the efficacy of selective 5-HT (serotonin) reuptake inhibitor (SSRI) antidepressants and may reverse stress-induced deficits in rodents., Experimental Approach: To further explore this hypothesis, we used mice lacking the 5-HT 3 receptor (Htr3a KO) and their wild-type (WT) controls to assess their response in behavioural paradigms relevant to anxiety and depression. Mice were studied under basal, antidepressant treatments and chronic social defeat stress (CSDS) conditions., Key Results: In basal conditions, Htr3a KO mice displayed anxiolytic- and antidepressant-like behaviours in the elevated plus maze, the social interaction and the forced swim tests (FST), but behaved as WT mice in response to acute citalopram in the FST. However, the effects of fluoxetine were blunted in Htr3a KO mice in these same tests. In an in vitro electrophysiological paradigm, a low-dose citalopram treatment triggered 5-HT 1A receptor desensitization only in the dorsal raphe nucleus of Htr3a KO, although a high dose desensitized 5-HT 1A autoreceptor function equally in Htr3a KO and WT mice, suggesting that citalopram may become effective at lower doses when 5-HT 3 receptors are inactivated. In addition, Htr3a deletion blocked CSDS-induced modification in the cortical expression of two genes involved in oxidative stress, CaMKIIa and SOD1., Conclusions and Implications: Taken together, these data show that Htr3a deletion promotes SSRI efficacy and prevents the occurrence of stress-induced deleterious effects, suggesting that the 5-HT 3 receptor may represent an interesting target for the treatment of stress-related disorders., (© 2017 The British Pharmacological Society.)

Background: Livedoid vasculopathy (LV) is a painful ulcerative condition involving white atrophy and livedo; a histopathologic feature seen is occlusive dermal vasculopathy. This may be associated with coagulation disorders such as hyperhomocysteinaemia (HHC)., Patients and Methods: We report the case of a 52-year-old woman presenting LV in which an abnormal scan image led us to diagnose coeliac disease. This enteropathy had caused vitamin B12 and folic acid deficiency, as well as HHC. Vitamin supplementation and a gluten-free diet resulted in complete healing of the lesions., Discussion: This case underlines the importance of screening for and correction of coagulation disorders in patients with LV. It also suggests that in the event of HHC, coeliac disease should be sought, even in the absence of gastrointestinal symptoms., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Serotonin plays a modulatory role in central control of the autonomic nervous system (ANS). The nucleus tractus solitarii (NTS) in the medulla is an area of viscerosomatic integration innervated by both central and peripheral serotonergic fibers. Influences from different origins therefore trigger the release of serotonin into the NTS and exert multiple influences on the ANS. This major influence on the ANS is also mediated by activation of several receptors in the NTS. In particular, the NTS is the central zone with the highest density of serotonin 3 (5-HT 3 ) receptors. In this review, we present evidence that 5-HT 3 receptors in the NTS play a key role in one of the crucial homeostatic responses to acute and chronic stress: inhibitory modulation of the parasympathetic component of the ANS. The possible functional interactions of 5-HT 3 receptors with GABA A and NK 1 receptors in the NTS are also discussed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Arterial oxygen desaturation frequently occurs in patients with COPD during daily activities at home. Oxygen flow is usually set at fixed and low rates for ambulatory patients. We evaluated an innovative closed-loop system (FreeO 2 ) that automatically adjusts the oxygen flow to the patient's needs in subjects with COPD during walking followed by recovery time, such as during ambulatory conditions., Methods: Patients with COPD who exhibited oxygen desaturation on exertion were included in the study. Subjects performed endurance shuttle walk tests followed by 10 min of recovery. The tests were conducted in a random order and in crossover with the 3 following conditions: subjects breathing (1) air at 2 L/min, (2) oxygen at 2 L/min, or (3) FreeO 2 (variable oxygen flow). S pO2 , pulse rate, P ETCO 2 , breathing frequency, and oxygen flow were continuously recorded during the 3 conditions. The primary outcome was the percentage of time within the S pO2 target of 92-96%. Secondary outcomes included the endurance shuttle walk test time and distance., Results: Sixteen subjects with COPD were recruited. The percentage of time with S pO 2 in the target range (92-96%) was higher while using the FreeO 2 , and time with severe oxygen desaturation (S pO 2 <88%) was lower with FreeO 2 in comparison with constant-flow oxygen and air testing conditions (0.6% vs 23.9% vs 52.2%, P < .001). In comparison with air, walking distance was increased by 35% with oxygen (P = .045) and by 63% with FreeO 2 (P < .001). The walking distance was increased by 17% with FreeO 2 in comparison with constant oxygen, but the difference was not statistically significant (P = .22)., Conclusions: Automatic titration of oxygen flow during walking to maintain oxygen saturation in a specified range improves oxygenation and may improve exercise tolerance during daily activity, such as walking, in patients with COPD in comparison with room air and fixed oxygen administration. (ClinicalTrials.gov registration: NCT02150434.)., (Copyright © 2016 by Daedalus Enterprises.)

Repeated social defeat in the rat induces long-lasting cardiovascular changes associated with anxiety. In this study, we investigated the effects of repeated social defeat on breathing. Respiratory rate was extracted from the respiratory sinus arrhythmia (RSA) peak frequency of the ECG in rats subjected to social defeat for 4 consecutive days. Respiratory rate was recorded under anesthesia 6 days (D+10) or 26 days (D+30) after social defeat. At D+10, defeated (D) rats spent less time in the open arms of the elevated plus maze test, had heavier adrenal glands, and displayed bradypnea, unlike nondefeated animals. At D+30, all signs of anxiety had disappeared. However, one-half of the rats still displayed bradypnea (DL rats, for low respiratory rate indicated by a lower RSA frequency), whereas those with higher respiratory rate (DH rats) had recovered. Acute blockade of the dorsomedial hypothalamus (DMH) or nucleus tractus solitarii (NTS) 5-HT3 receptors reversed bradypnea in all D rats at D+10 and in DL rats at D+30. Respiratory rate was also recorded in conscious animals implanted with radiotelemetric ECG probes. DH rats recovered between D+10 and D+18, whereas DL rats remained bradypneic until D+30. In conclusion, social stress induces sustained chronic bradypnea mediated by DMH neurons and NTS 5-HT3 receptors. These changes are associated with an anxiety-like state that persists until D+10, followed by recovery. However, bradypnea may persist in one-half of the population up until D+30, despite apparent recovery of the anxiety-like state., (Copyright © 2016 the American Physiological Society.)

Nicorandil, a nicotinamide ester, was first reported to be involved in the induction of oral ulcers in 1997. Since then, many reports of single or multiple nicorandil-induced ulcerations (NIUs) have been reported. We hypothesised that in the case of high-dosage nicorandil or after an increased dosage of nicorandil, nicotinic acid and nicotinamide (two main metabolites of nicorandil) cannot appropriately merge into the endogenous pool of nicotinamide adenine dinucleotide/phosphate, which leads to abnormal distribution of these metabolites in the body. In recent or maintained trauma, nicotinamide increases blood flow at the edge of the raw area, inducing epithelial proliferation, while nicotinic acid ulcerates this epithelial formation, ultimately flooding the entire scar. We demonstrate, by comparison to a control patient non-exposed to nicorandil, an abnormal amount of nicotinic acid (×38) and nicotinamide (×11) in the ulcerated area in a patient with NIUs. All practitioners, especially geriatricians, dermatologists and surgeons, must be aware of these serious and insidious side effects of nicorandil. It is critical to rapidly reassess the risk-benefit ratio of this drug for any patient, and not only for those with diverticular diseases., (© 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Recording of breathing frequency is a basic requirement for respiratory physiology. Usual techniques are invasive and constraining. Respiratory sinus arrhythmia (RSA) has recently been demonstrated to be a simple way to obtain respiration frequency at rest. In this study, we investigated whether this correlation is also observed during activity. We first compared RSA to the respiration frequency obtained in anesthetized rats using a pneumotachograph connected to the trachea (TRF). Data analyses using Passing and Bablok regression confirmed the absence of bias and proportional differences. Accordingly, the Bland-Altman plot did not show any significant differences in data sets. In a second experiment, we compared RSA to the respiration frequency obtained in freely moving rats using a subpleurally inserted telemetric catheter (PRF). Comparisons between RSA and PRF revealed no significant difference in determination of respiratory rate with the two methods, although the bias and confidence interval were greater when activity increased. This was, however, not the case during short episodes of sniffing-like tachypnea, during which no matching RSA peaks were observed. In conclusion, RSA frequency reflected regular respiration frequency independently of the level of activity and appears to be a good surrogate to usual techniques., (Copyright © 2015 the American Physiological Society.)

Lichen sclerosus et atrophicus (LSA) is an inflammatory disease that affects the genitals, which was first described by Hallopeau in 1887 and is of unknown etiology. Only 15% of patients have an associated extra-genital form, and 2.5% have an isolated extra-genital form. LSA treatment remains poorly codified and mostly empirical. Here, we report a case of LSA, of mainly cutaneous form, which was effectively treated using extracorporeal photochemotherapy (ECP). Remission was achieved quickly, after the fourth session, with excellent treatment tolerance. ECP is now recognized as an effective treatment for erosive lichen planus, graft-versus-host disease (GVHD), and scleroderma. Thus, we began ECP treatment for our cases of LSA based on clinical and/or anatomopathological similarities between LSA and these commonly ECP-treated disorders. The fact that ECP is effective in LSA, GVHD, erosive lichen planus, and scleroderma strengthen the hypothesis that there is a common link between these four conditions., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Anxiety disorders in humans reduce both the heart rate variability (HRV) and the sensitivity of the cardiac baroreflex (BRS). Both may contribute to sudden death. To elucidate the mechanisms underlying these alterations, male rats were subjected to social defeat sessions on four consecutive days. Five days later, the rats were found to be in an anxiety-like state. At this time point, we analysed HRV and BRS in the defeated rats, with or without treatment with the anxiolytic chlordiazepoxide (CDZ). HRV was reduced after social defeat, due to changes in the autonomic balance favouring the sympathetic over the parasympathetic component. Spontaneous and pharmacological baroreflex gains were also reduced. CDZ abolished anxiety-like symptoms as well as HRV and BRS alterations. Inhibition of the dorsomedial hypothalamus (DMH) with muscimol reversed all cardiovascular alterations, whereas blockade of the nucleus tractus solitarii (NTS) 5-HT3 receptor by the local or systemic administration of granisetron restored only baroreflex gains and the parasympathetic component of HRV. In conclusion, repeated social defeat in the rat lead to an anxiety-like state that was associated with lasting reduction in HRV and baroreflex gains. The DMH and the NTS were responsible for these chronic cardiovascular alterations. These regions may therefore constitute new therapeutic targets for reducing cardiac dysfunction and fibrillation in anxiety disorders.

Quadriceps muscle weakness and increased fatigability are well described in patients with chronic obstructive pulmonary disease (COPD). Whether these functional alterations also exist in distal leg muscles in patients with COPD is uncertain. Fifteen patients with COPD and 15 aged-matched healthy controls performed a 12-minute standardized treadmill exercise during which a fixed total expense of 40 Kcal was reached. The strength of i) dorsiflexors, ii) plantar flexors and iii) quadriceps was assessed at rest and after exercise using maximal voluntary contraction (MVC) and potentiated twitch force (Twpot). Resting MVC and Twpot were significantly lower in patients with COPD when compared with controls respectively for i) dorsiflexors (24.9 ± 8.4 vs. 31.2 ± 8.5 Nm, p < 0.05 and 4.3 ± 1.3 vs. 5.7 ± 1.8 Nm, p < 0.05), ii) plantar flexors (49.5 ± 11.8 vs. 62.1 ± 19.6 Nm, p < 0.05 and 10.8 ± 3.5 vs. 13.4 ± 2.7 Nm, p < 0.05), and iii) quadriceps muscles. There was a greater force loss in the distal leg muscles 15 minutes post-exercise in patients with COPD, while the strength of the quadriceps muscle remained stable in both groups. Patients with COPD had weaker dorsiflexor and plantar flexor muscles when compared to age-matched healthy controls. In addition, when exposed to the same absolute walking task, the fatigability of the distal leg muscles was higher in patients with COPD.

Rationale: We examined the responsiveness of a 3-minute constant rate shuttle walking protocol to detect improvements in exertional dyspnea following acute bronchodilation in COPD. Our hypothesis was that the 3-minute constant rate shuttle walking protocol would be able to adequately put forth improvements in exertional dyspnea following acute bronchodilation in this population., Methods: Using a placebo controlled, double-blind cross-over design, 39 patients with moderate to severe COPD performed a 3-min constant rate shuttle walking test during which they were asked to walk on a flat corridor at a speed that was externally imposed by an audio signal. During the test, dyspnea was graded using the 10-point modified Borg scale. The test was performed twice, following the administration of saline placebo or of 500 μg nebulized ipratropium bromide., Results: Improvements of respiratory pattern (respiratory rate and tidal volume) and statistically and clinically significant reductions in Borg dyspnea scores (∆ dyspnea score = 1.0 ± 0.2, p < 0.01) were seen during the 3-min shuttle walking protocol with ipratropium bromide compared to placebo., Conclusion: This 3-minute shuttle walking protocol adequately detected dyspnea and breathing pattern improvements following acute bronchodilation in COPD.

The primary objective of this study was to evaluate the effects of a 3-week treatment with tiotropium on walking capacity in chronic obstructive pulmonary disease (COPD). After familiarisation with study procedures, 36 patients were randomised to receive tiotropium 18 μg once daily or a matching placebo in a double-blind, parallel-group study. Pre- (trough) and 2-h post-dose pulmonary function was measured. An endurance shuttle walk was then completed. The same procedures were repeated after 3 weeks of treatment. Ventilatory parameters were monitored during exercise. At 3 weeks, tiotropium significantly improved walking endurance time in comparison with placebo, with a mean±sd between-group difference of 128±141 s (p=0.017). At 3 weeks, trough values for forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC) were significantly improved with tiotropium in comparison with placebo. The post-dose response to tiotropium was statistically superior to placebo after the first dose and after 3 weeks of treatment for FEV(1), FVC and inspiratory capacity. Ventilation and tidal volume at the end of walking were significantly improved with tiotropium. 3 weeks of tiotropium resulted in a greater walking endurance in patients with COPD. Improvements in FEV(1), maximal ventilation and tidal volume may contribute to this enhanced exercise capacity.

Background: Primary cutaneous diffuse B-cell lymphoma, leg type, are rare and aggressive tumours frequently affecting elderly patients. We present a case of a 53-year-old woman with an atypical presentation of primary cutaneous diffuse B-cell lymphoma, leg type., Case Report: Eight years after complete excision of a Jessner-Kanof lymphocytic infiltration on the right shoulder, the patient developed a primary cutaneous diffuse B-cell lymphoma, leg type at the same site. The isolated lesion was treated using local radiotherapy. One year later, the patient presented headache associated with a temporal lesion, and biopsy confirmed a relapse. Cerebral CT scan showed an osteolytic temporal lesion while the other investigations revealed no extracutaneous extension. She was treated with R-CHOP chemotherapy and intrathecal methotrexate due to the osteolytic lesion., Discussion: The particularity of this case consists in the age of this woman, who was younger than the average, the two atypical localizations on the shoulder, then the temple, and osteolysis, which is not the most frequent extension. Furthermore, to our knowledge, transformation of a Jessner-Kanof lesion into local aggressive primary cutaneous diffuse B-cell lymphoma, leg type, has not been yet described., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Rationale: The endurance time (T(end)) during constant-workrate cycling exercise (CET) is highly variable in COPD. We investigated pulmonary and physiological variables that may contribute to these variations in T(end)., Methods: Ninety-two patients with COPD completed a CET performed at 80% of peak workrate capacity (W(peak)). Patients were divided into tertiles of T(end) [Group 1: <4 min; Group 2: 4-6 min; Group 3: >6 min]. Disease severity (FEV(1)), aerobic fitness (W(peak), peak oxygen consumption [VO2(peak)], ventilatory threshold [VO2(VT)]), quadriceps strength (MVC), symptom scores at the end of CET and exercise intensity during CET (heart rate at the end of CET to heart rate at peak incremental exercise ratio [HR(CET)/HR(peak)]) were analyzed as potential variables influencing T(end)., Results: W(peak), VO2(peak), VO2(VT), MVC, leg fatigue at end of CET, and HR(CET)/HR(peak) were lower in group 1 than in group 2 or 3 (p≤0.05). VO2(VT) and leg fatigue at end of CET independently predicted T(end) in multiple regression analysis (r = 0.50, p = 0.001)., Conclusion: T(end) was independently related to the aerobic fitness and to tolerance to leg fatigue at the end of exercise. A large fraction of the variability in T(end) was not explained by the physiological parameters assessed in the present study. Individualization of exercise intensity during CET should help in reducing variations in T(end) among patients with COPD.