Reverse Lip Lift For Deep Face Burn Sequelae With Bilateral Nostril Stenosis And Lip Contracture: An Original Technique. A Case And Literature Review.

Bilateral nostril stenosis resulting from deep facial burn that occurred on an oxygen-requiring patient with tobacco use is life threatening with obstruction of the airway and impossibility of oxygen supplementation use. We report the case of a deep burn involving the nose and the upper lip during oxygen and tobacco use with a severe bilateral nostril stenosis and upper lip retraction. We did a reverse bullhorn lip lift with bilateral alar base transposition realized in a one-stage surgery with nasal conformer for 4 months. Surgery allowed a significant opening of the nostril stenosis with a 9mm and 11mm major axis on the right and left side respectively. It brought restoration of the ability to nose breath and use an oxygen device, and was considered satisfactory by the patient and the operators. There was no recurrence at 18-month follow-up. Literature provides few examples of management of severe bilateral nostril stenosis following facial deep burn. Nasal conformers with progressive diameter augmentation, rhinoplasty procedure, local plasties, dermal flap, skin and composite grafts can treat this situation but there is no gold standard procedure. Reverse bullhorn lip lift with bilateral alar base transposition makes it possible to correct this severe deep burn sequela. With this clinical case, we show the possibility to treat it in a one-stage procedure through an aesthetic procedure inspiration, with an acceptable scar on the donor site.

La survenue d'une sténose narinaire bilatérale après une brûlure profonde de la face, chez un patient oxygénodépendant et fumeur, impacte le pronostic vital, par obstruction des voies aériennes supérieures et impossibilité d'utiliser l'oxygénothérapie. Nous rapportons le cas d'une brûlure profonde du nez et de la lèvre supérieure survenue en fumant pendant l'oxygénothérapie, entraînant une importante sténose narinaire bilatérale et une rétraction de la lèvre supérieure. Nous avons réalisé un lifting labial en corne de buffle inversé avec transposition bilatérale des ailes narinaires en un seul temps opératoire. Un conformateur narinaire a été porté pendant quatre mois. Cette chirurgie a permis une ouverture significative des sténoses narinaires, avec 9 mm et 11 mm de grand axe transversal respectivement à droite et à gauche. Cela a permis de restaurer la fonction respiratoire nasale et de permettre le port du masque à oxygène. Le résultat a été jugé satisfaisant par le patient et par les opérateurs. Nous n'avons pas noté de récidive à 18 mois de la chirurgie. La littérature rapporte peu de cas de sténose narinaire bilatérale après brûlure profonde de la face. Des conformateurs narinaires de diamètre progressivement croissant, des techniques type rhinoplastie, des plasties locales, des lambeaux cutanés, des greffes cutanées ou composites ont été décrites mais il n'y a pas de consensus. La technique de lifting labial en corne de buffle inversé associée à une transposition des ailes narinaires nous a permis de traiter ces séquelles de brûlure profonde. À travers ce cas cliniques, nous montrons la possibilité de traitement en un temps par une technique inspirée des techniques de chirurgie esthétique et avec un résultat cicatriciel acceptable.

The combination of deep breathing and mental imagery promotes cardiovascular recovery in firefighters.

Firefighters' rescue operations involve intense physical activity associated with a high level of cardiovascular stress. To sustain such intense physical performance whilst maintaining a healthy heart, it is crucial that they benefit from rapid recovery between each intervention. This study aimed at investigating the impacts of a recovery protocol combining deep breathing and mental imagery. Forty firefighters were divided into two experimental groups which undertook two maximum fitness tests separated by either the control recovery protocol (30 min reading time; n = 20) or the experimental recovery protocol (30 min of deep breathing and mental imagery; n = 20). When compared to the pre-tests, the percentage evolution ratios in the post-tests for the Cooper performance, the heart rate recovery and the parasympathetic reactivation were promoted by the experimental protocol, compared to simple reading. In light of these results, we propose the use of practices of deep-breathing combined with mental imagery to improve firefighters' recovery. Practitioner summary: Firefighters' activities involve intense physical activities associated with a high level of psychological stress. Enhancing their recovery after each rescue intervention appears crucial. The results of this study showed that a recovery protocol combining deep breathing and mental imagery promotes heart rate recovery and better maintenance of physical fitness.

[Use of methoxyflurane on acute pain during burn dressing in adult consultation]. / Utilisation du méthoxyflurane sur la douleur aiguë lors du pansement en consultation des brûlés adultes.

INTRODUCTION: The objective was to compare the short-term efficacy of methoxyflurane vs. MEOPA on acute pain during burn dressing in consultation, the secondary outcome was to assess the patient's comfort and the quality of the dressing performed. MATERIALS AND METHODS: Monocentric, prospective study from April 2018 to January 2019. Men and women>18 years presenting acute burn on<10% SCT were included. A pain≥4 on the numerical scale (from 0 to 10) at the beginning of the treatment established the indication of methoxyflurane or MEOPA, with randomization done by a nurse. The following data were collected: burn description, performed debridement, pain assessment by numerical scale: on arrival, at the beginning of care, after 6 to 10 inhalations for methoxyflurane or 3 to 4minutes of inhalation for MEOPA and at the end of care. RESULTS: Sixty patients were included, 30 in each group. There was a decrease of -2.47 points of numerical scale when initiating methoxyflurane against -1.53 points for MEOPA (P=0.08). Patients were significantly less painful when stopping treatment in the methoxyflurane group -4 points vs -2 points (P=0.001). Methoxyflurane significantly improved the debridement of the burn (P=0.018). CONCLUSION: Methoxyflurane is more effective than MEOPA in acute pain in burn dressing, improved patient comfort, and improved dressing quality.

Does the repetition over a short time of a microsurgical suture improve its reliability?

Our hypothesis was that immediate repetition of a microsurgery-suturing task will improve its execution and outcome. This was an experimental animal study. Ten surgeons were divided into two groups of five surgeons. Each performed two end-to-end carotid anastomoses on the same rat, one after the other. The anastomosis was evaluated by the surgeon and an instructor. The primary endpoint was permeability. The outcome was evaluated using an objective and subjective assessment grid yielding 1 to 3 points per item. The total scores for each of the 10 surgeons were used to compare the anastomosis of carotid 1 versus 2, using the ratings given by the surgeon and the instructor. Twenty anastomoses were performed, but 1 rat died intraoperatively, leaving 18 anastomoses for evaluation. No significant differences were found on the main endpoint of permeability, with all anastomoses being permeable. The surgeon's self-assessment was significantly better for the second carotid artery (P=0.05), but this was not confirmed by the proxy assessment (instructor). The analysis by subgroups-morning versus afternoon-found the second carotid anastomosis was significant better in the self-assessment and proxy assessment for the morning group (P<0.001, P=0.024). There was no significant difference in clamping times. The immediate repetition of a microsurgical procedure seems to favor its execution, which leads us to propose that the more difficult or important anastomosis should be done after an easier or less important one during complex surgeries. LEVEL OF EVIDENCE: 2B.

Distinct Profiles of Consumers of Psychoactive Substances in People Attending French Sexual Transmitted Infections Centers.

The objective of this cross-sectional survey was to assess the prevalence of psychoactive substance use (PSU) in people attending 11 French Sexual Transmitted Infection Centers, and to specify their profiles (PSU and link with risky sexual behaviors) using the ascending hierarchical clustering method. Among the 5220 individuals who completed the survey, 55.6% were men and the median age was 24 years [IQR: 20-31]. Among the participants, 2751 (52.7%) reported PSU at least once in their life. Ascending hierarchical clustering identified seven distinct profiles of participants based on their PSU. This study shows a high prevalence of PSU and alcohol consumption in this young population. Moreover, subgroup analysis allowed identifying groups of psychoactive substance users who presented specific risks or vulnerabilities and who should be priority targets for interventions, particularly sexual minority groups.

c-Jun N-terminal kinase 2 promotes enterocyte survival and goblet cell differentiation in the inflamed intestine.

c-Jun N-terminal kinases (JNKs) contribute to immune signaling but their functional role during intestinal mucosal inflammation has remained ill defined. Using genetic mouse models, we characterized the role of JNK1 and JNK2 during homeostasis and acute colitis. Epithelial apoptosis, regeneration, differentiation, and barrier function were analyzed in intestinal epithelium-specific (ΔIEC) or complete JNK1 and bone marrow chimeric or complete JNK2 deficient mice as well as double-knockout animals (JNK1ΔIECJNK2-/-) during homeostasis and acute dextran sulfate sodium (DSS)-induced colitis. Results were confirmed using human HT-29 cells and wild-type or JNK2-deficient mouse intestinal organoid cultures. We show that nonhematopoietic JNK2 but not JNK1 expression confers protection from DSS-induced intestinal inflammation reducing epithelial barrier dysfunction and enterocyte apoptosis. JNK2 additionally enhanced Atonal homolog 1 expression, goblet cell and enteroendocrine cell differentiation, and mucus production under inflammatory conditions. Our results identify a protective role of epithelial JNK2 signaling to maintain mucosal barrier function, epithelial cell integrity, and mucus layer production in the event of inflammatory tissue damage.

Developmental determinants in non-communicable chronic diseases and ageing.

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

Thick collagen-based 3D matrices including growth factors to induce neurite outgrowth.

Designing synthetic microenvironments for cellular investigations is a very active area of research at the crossroads of cell biology and materials science. The present work describes the design and functionalization of a three-dimensional (3D) culture support dedicated to the study of neurite outgrowth from neural cells. It is based on a dense self-assembled collagen matrix stabilized by 100-nm-wide interconnected native fibrils without chemical crosslinking. The matrices were made suitable for cell manipulation and direct observation in confocal microscopy by anchoring them to traditional glass supports with a calibrated thickness of ∼50µm. The matrix composition can be readily adapted to specific neural cell types, notably by incorporating appropriate neurotrophic growth factors. Both PC-12 and SH-SY5Y lines respond to growth factors (nerve growth factor and brain-derived neurotrophic factor, respectively) impregnated and slowly released from the support. Significant neurite outgrowth is reported for a large proportion of cells, up to 66% for PC12 and 49% for SH-SY5Y. It is also shown that both growth factors can be chemically conjugated (EDC/NHS) throughout the matrix and yield similar proportions of cells with longer neurites (61% and 52%, respectively). Finally, neurite outgrowth was observed over several tens of microns within the 3D matrix, with both diffusing and immobilized growth factors.

Compartmentalized expression of Th1 and Th17 cytokines in pediatric inflammatory bowel diseases.

BACKGROUND: Interleukin (IL)-23, IL-17A, IL-17F, and interferon-gamma (IFN-γ) are important mediators of inflammatory colitis and are potential therapeutic targets in inflammatory bowel disease (IBD). Their expression profile in the different parts of normal noninflammatory intestine is unclear and their changes during pathology have not yet been addressed in pediatric IBD patients. METHODS: We quantified the transcriptional expression of IL-23, IL-12, IL-17A, IL-17F, IL-6, and IL-10 in healthy, noninflammatory duodenum, ileum, and colon and in inflamed and noninflamed biopsies of pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC). RESULTS: In healthy tissue, expression of IL-17A is highest in the ileum, with IFN-γ expression lowest in the colon. Compared to healthy sections, CD patients displayed increased IL-12p35 and IFN-γ levels in noninflamed ileum and colon, respectively. Modifications of cytokine expression between noninflamed and inflamed tissues was characterized by increased IL-17A in UC colon, IFN-γ in CD colon, and IL-17A, IFN-γ and IL-6 in CD ileum. Elevated IL-17A levels were positively correlated with IFN-γ in both inflammatory CD and UC but IL-17A and IFN-γ were correlated with IL-23p19 in CD ileum only. CONCLUSIONS: The expression of Th1 and Th17 cytokines varies along the intestine, indicating local specific regulation mechanisms. However, the cytokine expression patterns in the same tissue depends on the pathology, with a Th1 or a Th17 profile in the colon of CD and UC patients, respectively, and a Th1/Th17 profile in the ileum of CD patients. This indicates overlapping but distinct immune mechanisms driving intestinal inflammation in these two pathologies.

Coagulation factor X mediates adenovirus type 5 liver gene transfer in non-human primates (Microcebus murinus).

Coagulation factor X (FX)-binding ablated adenovirus type 5 (Ad5) vectors have been genetically engineered to ablate the interaction with FX, resulting in substantially reduced hepatocyte transduction following intravenous administration in rodents. Here, we quantify viral genomes and gene transfer mediated by Ad5 and FX-binding-ablated Ad5 vectors in non-human primates. Ad5 vectors accumulated in and mediated gene transfer predominantly to the liver, whereas FX-binding-ablated vectors primarily targeted the spleen but showed negligible liver gene transfer. In addition, we show that Ad5 binding to hepatocytes may be due to the presence of heparan sulfate proteoglycans (HSPGs) on the cell membrane. Therefore, the Ad5-FX-HSPG pathway mediating liver gene transfer in rodents is also the mechanism underlying Ad5 hepatocyte transduction in Microcebus murinus.

The grey mouse lemur: a non-human primate model for ageing studies.

The use of non-human primate models is required to understand the ageing process and evaluate new therapies against age-associated pathologies. The present article summarizes all the contributions of the grey mouse lemur Microcebus murinus, a small nocturnal prosimian primate, to the understanding of the mechanisms of ageing. Results from studies of both healthy and pathological ageing research on the grey mouse lemur demonstrated that this animal is a unique model to study age-dependent changes in endocrine systems, biological rhythms, thermoregulation, sensorial, cerebral and cognitive functions.

A systematic review of economic evaluation studies of tuberculosis control in high-income countries.

Tuberculosis (TB) is a leading cause of death in developing countries and an important health threat in the industrialised world. Ideally, interventions in TB control are effective, acceptable and economically attractive. This review summarises all economic evaluation studies of TB control in high-income countries over the last 20 years. We provide indications on the relative economic attractiveness of TB interventions based on the reported conclusions. A total of 118 studies using different economic evaluation methodologies on a wide range of TB interventions are included. Most studies (70%) were from North America, and about half (47%) concerned interventions among the general population. Even though the large majority of studies (85%) aimed at preventing active TB disease, 44% of these ignored the prevention of secondary infections, thereby under- estimating the benefits of the intervention. Choosing a health care instead of a societal perspective (92% vs. 8%) further underestimated the benefits. Moreover, 74 studies (62%) disregarded discounting, and for 9 of them this led to overestimated future costs. In all, 66% of the studies reported conclusions favouring the evaluated intervention, which is modest given that a publishing bias towards favourable results is to be expected. In conclusion, we demonstrate that many studies in this review have put the evaluated TB intervention at a disadvantage by the choice of methodology, i. e., underestimating benefits and overestimating costs. This may have led to an overly conservative approach to the introduction of new interventions in TB control.

Prevalence of meticillin-resistant Staphylococcus aureus amongst professional meat handlers in the Netherlands, March-July 2008.

In the Netherlands, meticillin-resistant Staphylococcus aureus (MRSA) is detected on pork and veal farms, and hence farmers working with MRSA-positive animals are at an increased risk of being colonised. Recently retail meat products have been found positive for MRSA. Therefore, we tested the prevalence of MRSA among employees who work in the cold meat processing industry and in institutional kitchens. Nasal swabs and samples from the employees' hands as well as the handled meat were tested quantitatively and qualitatively for the presence of MRSA. Typical colonies were confirmed by PCR and typed using multi-locus sequence typing and spa­typing. All samples taken from 95 employees tested negative for MRSA, but 31 carried MSSA. From meat, five of 35 samples were positive for MRSA, containing between 0.01 and more than 10 bacteria per gram. The risk for professionals of MRSA colonisation from handling raw meat was therefore low in our setting, suggesting that the general population is at an even lower risk of being infected through meat handling.

[What the cardiologist should know about physical training]. / Ce que le cardiologue doit savoir sur l'entraînement sportif.

Because of the cardiovascular stresses and the potential risks of physical training, cardiologists are often asked to give an opinion on aptitude for sport. It is therefore important to understand the fundamentals of physical training. This is based on specific rules; general physical preparation, progressive nature of the activity, individualisation of training programmes, specificity of sporting activity, recovery times and planning of exercise. The two main types of training (aerobics and weight training) are used preferentially according to the type of sport but good aerobic capacity is required in all specialities. The training implies a certain physical stress and the individual has his own limitations. The cardiologist may help identify an imbalance between the two without being an expert in all sporting disciplines. In this field, the physician is no substitute for the coach but can help in managing the sportsman's health.

[Anti-TNF alpha monoclonal antibodies (infliximab) and tuberculosis: apropos of 3 cases]. / Anticorps anti-TNF alpha (infliximab) et tuberculose: à propos de trois cas.

INTRODUCTION: Monoclonal TNF alpha antibodies are a new treatment of severe rheumatoid arthritis. One of the possible side effects is the appearance of opportunistic infections. We report here on three cases of disseminated tuberculosis observed in patients undergoing treatment with infliximab. EXEGESIS: A 45-year-old woman, treated with infliximab, was hospitalised after five infusions for fever and dyspnoea. The exams showed pulmonary and peritoneal tuberculosis. The second case is a 75-year-old woman whose symptoms were fever, cough and cervical adenopathy after three infliximab infusions. Diagnosis was disseminated tuberculosis. The third case is a 59-year-old man who was hospitalised for an infectious syndrome with dyspnoea, after two infliximab infusions. We discovered pulmonary tuberculosis. CONCLUSION: These three cases added to the 68 cases of tuberculosis registered with the treatment of infliximab. This confirms the risk of severe opportunist infectious side effects. TNF alpha is a cytokine which has anti-infectious properties. These tuberculoses are severe and generalized. It is recommended to search for an active or latent tuberculosis before beginning treatment with infliximab, and to check these patients frequently.

Three-dimensional structure of the lithostathine protofibril, a protein involved in Alzheimer's disease.

Neurodegenerative diseases are characterized by the presence of filamentous aggregates of proteins. We previously established that lithostathine is a protein overexpressed in the pre-clinical stages of Alzheimer's disease. Furthermore, it is present in the pathognomonic lesions associated with Alzheimer's disease. After self-proteolysis, the N-terminally truncated form of lithostathine leads to the formation of fibrillar aggregates. Here we observed using atomic force microscopy that these aggregates consisted of a network of protofibrils, each of which had a twisted appearance. Electron microscopy and image analysis showed that this twisted protofibril has a quadruple helical structure. Three-dimensional X-ray structural data and the results of biochemical experiments showed that when forming a protofibril, lithostathine was first assembled via lateral hydrophobic interactions into a tetramer. Each tetramer then linked up with another tetramer as the result of longitudinal electrostatic interactions. All these results were used to build a structural model for the lithostathine protofibril called the quadruple-helical filament (QHF-litho). In conclusion, lithostathine strongly resembles the prion protein in its dramatic proteolysis and amyloid proteins in its ability to form fibrils.

Lithostathine and pancreatitis-associated protein are involved in the very early stages of Alzheimer's disease.

According to one of the theories formulated to explain the etiology of Alzheimer's disease (AD), amylosis may reflect a specific inflammatory response. Two inflammatory proteins, lithostathine and PAP, were evidenced by immunohistochemistry in senile plaques and neurofibrillary tangles of patients with AD. In addition, lithostathine and PAP were significantly increased in the cerebrospinal fluid of patients with AD when compared to patients with multiple sclerosis, another inflammatory disease, and to normal control subjects. However, no correlation was observed with age of occurrence. Furthermore, lithostathine and PAP were increased even at the very early stages of AD, and their level remained elevated during the course of the AD unlike TNFalpha whose level, very high at very early stages, regularly decreased. Finally, if part of lithostathine and PAP are synthesized in the brain, a large part comes from serum by passage over the blood-brain barrier. These results indicate (i) the existence of an acute phase response followed by a chronic inflammation in AD, and (ii) that lithostathine and PAP are involved even at the first pre-clinical biochemical events of AD. In addition, because lithostathine undergoes an autolytic cleavage leading to its precipitation and the formation of fibrils, we believe that it may be involved in amyloidosis and tangles by allowing heterogeneous precipitation of other proteins.

[Long-term treatment of Alzheimer's disease: followup of a cohort of 255 patients treated with lacrine for four years]. / Traitement de la maladie d'Alzheimer au long cours: à propos d'une cohorte de 255 patients traités quatre ans par tacrine.

We describe the follow-up of a cohort of 255 Alzheimer's disease (AD) patients (81 males, 174 females) treated by tacrine during 4 years. We performed the survey of hepatic, cholinergic and general tolérance. Drug efficacy was measured by MMS examination on weeks 0, 18, 30, 52, 104, 156 and 208. A total of 190 patients (74.5 percent) were dropped out of this study, 75 (29 percent) for adverse events. We found 85 hepatic (33 percent), 79 cholinergic (31 percent), 31 (12 percent) neuropsychiatric and 72 general (28 percent) side effects. In term of drug efficacy we observed a global decline of 2.5 MMS points during the first year and 2 MMS points between W52 and W156. Tacrine's symptomatic efficacy, defined as the number of patients improved or stabilized at W30, was present in 50 patients (46 percent) among the 109 patients reaching W30. The intensity of symptomatic efficacy was expressed by a 2.7 MMS points increase in 37 patients improved on W30. The long term effects of Tacrine, measured by the MMS score at one year, showed a positive impact as the MMS was 2.5 points above the expected score in non treated AD patients. This study raises the practical problem of optimal cholinesterase inhibitors use in AD and the theoretical question of long term action of cholinesterase inhibitors on cerebral lesions of AD.

Association of APOE promoter but not A2M polymorphisms with risk of developing Alzheimer's disease.

The APOE4 allele is widely accepted as a major risk factor for late-onset Alzheimer's disease (AD). Recently, it has been reported that polymorphisms in the APOE promoter and in the alpha2-macroglobulin gene (A2M) are associated with AD. We have analyzed the distribution of APOE alleles, -219T/G APOE promoter polymorphism, and A2M/A2Mdel polymorphism in a large case-control study. Our results showed that APOE genotype was the only informative marker of AD risk contrary to -219T/G and A2M/A2Mdel polymorphism. In AD patients however, a strong linkage disequilibrium was observed between the T allele of -219T/G polymorphism and APOE4 allele. This result indicates that -219T/G APOE promoter polymorphism is a risk factor for AD by increasing the APOE4-associated risk.