Corticospinal and spinal excitability during peripheral or central cooling in humans.

Cold exposure can impair fine and gross motor control and threaten survival. Most motor task decrement is due to peripheral neuromuscular factors. Less is known about cooling on central neural factors. Corticospinal and spinal excitability were determined during cooling of the skin (Tsk) and core (Tco). Eight subjects (four female) were actively cooled in a liquid perfused suit for 90 min (2 °C inflow temperature), passively cooled for 7 min, and then rewarmed for 30 min (41 °C inflow temperature). Stimulation blocks included 10 transcranial magnetic stimulations [eliciting motor evoked potentials (MEPs) which indicate corticospinal excitability], 8 trans-mastoid electrical stimulations [eliciting cervicomedullary evoked potentials (CMEPs) which indicate spinal excitability] and 2 brachial plexus electrical stimulations [eliciting maximal compound motor action potentials (Mmax)]. These stimulations were delivered every 30 min. Cooling for 90 min reduced Tsk to 18.2 °C while Tco did not change. At the end of rewarming Tsk returned to baseline while Tco decreased by 0.8 °C (afterdrop) (P < 0.001). Metabolic heat production was higher than baseline at the end of passive cooling (P = 0.01), and 7 min into rewarming (P = 0.04). MEP/Mmax remained unchanged throughout. CMEP/Mmax increased by 38% at end cooling (although increased variability at this time rendered the increase insignificant, P = 0.23) and 58% at end warming when Tco was 0.8 °C below baseline (P = 0.02). Cooling increased spinal excitability but not corticospinal excitability. Cooling may decrease cortical and/or supraspinal excitability which is compensated for by increased spinal excitability. This compensation is key to providing a motor task and survival advantage.

[Screening for diabetic retinopathy in the Centre-Val de Loire region: A study based on the French national healthcare database]. / Suivi ophtalmologique des patients diabétiques en région Centre-Val de Loire : une étude issue du Système national des données de santé (SNDS).

INTRODUCTION: The main objective of this study was to investigate the rate of ophthalmological screening for diabetic retinopathy in diabetic individuals in the Centre-Val de Loire (CVDL) region. This study secondarily aimed to identify factors associated with regular ophthalmological screening. MATERIAL AND METHODS: Data were extracted from the French national healthcare database (SNDS). Individuals were identified on the basis of reimbursements for antidiabetic medications. Patients who were identified as having at least one reimbursed eye examination between 2015 and 2016 were considered as having regular follow-up. RESULTS: In total, 118,181 diabetic individuals residing in CVDL were identified in the SNDS, and 74,048 had undergone ophthalmological screening. The rate of eye examination was 62.7% between 2015 and 2016 and was highly variable within the region (from 65.6% in Loiret to 54.0% in Cher). The main factors associated with regular eye screening were: follow-up with an established primary care physician (OR=2.88), regular follow-up with a diabetologist (OR=2.14), and regular follow-up with an internist (OR=1.57). CONCLUSION: This study suggests that ophthalmological screening for diabetic retinopathy in individuals with diabetes in the CVDL region could be significantly improved, particularly in rural areas. Factors influencing compliance with follow-up are multiple but appear mainly related to the patients' quality of overall medical management. These findings highlight the need for public health policies to improve detection and prevention of diabetic retinopathy by promoting comprehensive medical care for diabetic individuals.

Colonization with Helicobacter is concomitant with modified gut microbiota and drastic failure of the immune control of Mycobacterium tuberculosis.

Epidemiological and experimental observations suggest that chronic microbial colonization can impact the immune control of other unrelated pathogens contracted in a concomitant or sequential manner. Possible interactions between Mycobacterium tuberculosis infection and persistence of other bacteria have scarcely been investigated. Here we demonstrated that natural colonization of the digestive tract with Helicobacter hepaticus in mice is concomitant with modification of the gut microbiota, subclinical inflammation, and drastic impairment of immune control of the growth of subsequently administered M. tuberculosis, which results in severe lung tissue injury. Our results provided insights upon the fact that this prior H. hepaticus colonization leads to failures in the mechanisms that could prevent the otherwise balanced cross-talk between M. tuberculosis and the immune system. Such disequilibrium ultimately leads to the inhibition of control of mycobacterial growth, outbreak of inflammation, and lung pathology. Among the dysregulated immune signatures, we noticed a correlation between the detrimental lung injury and the accumulation of activated T-lymphocytes. Our findings suggest that the impact of prior Helicobacter spp. colonization and subsequent M. tuberculosis parasitism might be greater than previously thought, which is a key point given that both species are among the most frequent invasive bacteria in human populations.

Combined impacts of global changes on biodiversity across the USA.

Most studies of the effects of global changes on biodiversity focus on a single threat, but multiple threats lead to species extinction. We lack spatially explicit assessments of the intensity of multiple threats and their impacts on biodiversity. Here, we used a novel metric of cumulative threats and impacts to assess the consequences of multiple threats on 196 endemic species across the USA. We predict that large areas with high cumulative impact scores for amphibians, birds, mammals, and reptiles will be concentrated in the eastern part of the USA by the 2050 s and 2080 . These high cumulative impact values are due mainly to the presence of invasive species, climate change, cropland and pasture areas; additionally, a significant proportion of endemic species are vulnerable to some of these threats where they occur. This analysis provides a useful means of identifying where conservation measures and monitoring programs that should consider multiple threats should be implemented in the future.

[How do residents in anesthesiology learn their future speciality? A resident satisfaction survey in the Northwest of France]. / Comment les anesthésistes-réanimateurs français apprennent-ils leur spécialité ? Une enquête de ressenti auprès des internes de l'inter-région Nord.

STUDY DESIGN: Opinion survey. OBJECTIVES: To know the level of satisfaction and the expectations of the residents in anesthesiology in the Northwest of France. MATERIALS AND METHODS: A standardized questionnaire assessing the theoretical and practical training was mailed to the 4th- and 5th-year anesthesiology residents (DESAR 4 and 5) in the Northwest of France over a 6-month period. Four items were studied: the profile of responders, the approval of theoretical and practical teaching, and the improvement propositions. RESULTS: The response rate was 61%. A change in speciality has never been looked for by 95% of residents. The training was considered as good or very good in 90% of cases. The elements of theoretical teaching are variably considered according to their merits. Practical training gave entire satisfaction whatever its type and place. Additional specific training in regional anesthesia, difficult intubation and echocardiography is required. Most DESAR would be interested in obtaining a post-internship job or a stage in private hospitals. DISCUSSION: Teaching generally meets the expectations of students. These regional data are similar with the results of French national surveys. They highlight the good quality of training but suggest it could be further improved. CONCLUSION: The homogeneity of teaching, based on the objectives proposed by the French College of Anesthesiologists, and the dynamism of the French Society of Anesthesiology and Critical Care Medicine ensures the quality of training for future specialists.

Three calcium-sensitive genes, fus, brd3 and wdr5, are highly expressed in neural and renal territories during amphibian development.

Numerous Ca(2+) signaling events have been associated with early development of vertebrate embryo, from fertilization to organogenesis. In Xenopus laevis, Ca(2+) signals are key regulators in the earliest steps of the nervous system development. If neural determination is one of the best-characterized examples of the role of Ca(2+) during embryogenesis, increasing literature supports a determining role of organogenesis and differentiation. In blastula the cells of the presumptive ectoderm (animal caps) are pluripotent and can be induced toward neural fate with an intracellular increase of free Ca(2+) triggered by caffeine. To identify genes that are transcribed early upon Ca(2+) stimuli and involved in neural determination, we have constructed a subtractive cDNA library between neuralized and non-neuralized animal caps. Here we present the expression pattern of three new Ca(2+)-sensitive genes: fus (fused in sarcoma), brd3 (bromodomain containing 3) and wdr5 (WD repeat domain 5) as they all represent potential regulators of the transcriptional machinery. Using in situ hybridization we illustrated the spatial expression pattern of fus, brd3 and wdr5 during early developmental stages of Xenopus embryos. Strikingly, their domains of expression are not restricted to neural territories. They all share a specific expression throughout renal organogenesis which has been found to rely also on Ca(2+) signaling. This therefore highlights the key function of Ca(2+) target genes in specific territories during early development. We propose that Ca(2+) signaling through modulation of fus, brd3 and wdr5 expressions can control the transcription machinery to achieve proper embryogenesis. This article is part of a Special Issue entitled: 12th European Symposium on Calcium.

Induction of protective immunity against Mycobacterium tuberculosis by delivery of ESX antigens into airway dendritic cells.

As the Bacillus Calmette-Guérin (BCG) vaccine does not confer long-lasting protection against lung Mycobacterium tuberculosis infection, the development of more efficient vaccines is greatly needed. Here, we used mycobacterial low-molecular weight proteins of the 6-kDa Early Secreted Antigenic Target (ESAT-6) protein family (ESX) antigens for the evaluation of a novel vaccine delivery strategy that enables versatile in vivo targeting of antigens into specialized dendritic cell (DC) subsets. ESX antigens were genetically fused to the tetramerizing core of streptavidin (SA) to form high-affinity complexes with biotin (biot)-conjugated antibodies recognizing DC surface receptors. When directed through the CD11b or CD11c ß2-integrins or diverse C-type lectins, the ESX-SA:biot-antibody complexes were efficiently captured and presented on major histocompatibility complex molecules of DCs to specific T-cell receptors. Robust ESX-specific T-cell responses were induced by immunization with as little as several picomoles of ESX-SA targeted to DC subsets. Moreover, directing of TB10.4-SA to airway CD205(+) cells enabled the induction of mucosal T-cell responses and provided significant protection against virulent M. tuberculosis.

Oral macrophage-like cells play a key role in tolerance induction following sublingual immunotherapy of asthmatic mice.

Sublingual allergen-specific immunotherapy (SLIT) is a safe and efficacious treatment for type 1 respiratory allergies. Herein, we investigated the key subset(s) of antigen-presenting cells (APCs) involved in antigen/allergen capture and tolerance induction during SLIT. Following sublingual administration, fluorochrome-labeled ovalbumin (OVA) is predominantly captured by oral CD11b⁺CD11c⁻ cells that migrate to cervical lymph nodes (CLNs) and present the antigen to naive CD4⁺ T cells. Conditional depletion with diphtheria toxin of CD11b⁺, but not CD11c⁺ cells, in oral tissues impairs CD4⁺ T-cell priming in CLNs. In mice with established asthma to OVA, specific targeting of the antigen to oral CD11b⁺ cells using the adenylate cyclase vector system reduces airway hyperresponsiveness (AHR), eosinophil recruitment in bronchoalveolar lavages (BALs), and specific Th2 responses in CLNs and lungs. Oral CD11b⁺CD11c⁻ cells resemble tolerogenic macrophages found in the lamina propria (LP) of the small intestine in that they express the mannose receptor CD206, as well as class-2 retinaldehyde dehydrogenase (RALDH2), and they support the differentiation of interferon-γ/interleukin-10 (IFNγ/IL-10)-producing Foxp3⁺ CD4⁺ regulatory T cells. Thus, among the various APC subsets present in oral tissues of mice, macrophage-like cells play a key role in tolerance induction following SLIT.

Medicoeconomic study of microsurgical head and neck reconstructions.

OBJECTIVES: The use of microanastomosed free flaps has become essential in the management of head and neck defects following cancer resection or other causes. However, this surgery is under-rated by the French case-mix based rating procedure. The purpose of this study was to evaluate the cost balance of this type of surgery in a patient cohort managed by free flap head and neck reconstruction in a polyvalent adult head and neck surgery department. MATERIAL AND METHODS: This retrospective study was based on 52 patients divided into two groups undergoing either mandibular or nonmandibular reconstruction. Possible prognostic factors were investigated in patients undergoing mandibular reconstruction. Kaplan-Meier survival analysis was also performed for both groups of patients. The Foch Hospital financial department's analytical accounting data for 2006 and 2007 were used to evaluate the costs related to these patients. A senior surgeon retrospectively reviewed the patients' charts with the Medical Informatics physician in order to optimize the choice of diagnosis-related group (DRG). RESULTS: The mean income generated by mandibular and nonmandibular reconstructions in 2006 and 2007 was 545€/day and 526€/day for hospitalisation including free flap and 828€/day and 818€/day for "satellite" hospitalisations for other procedures related to the reconstruction, respectively. After review of the rating by a senior surgeon, in order to optimize the choice of DRG, the mean income received by the hospital could have been improved by +6%. CONCLUSION: Optimization of procedure and hospital stay rating associated with better collaboration with the Medical Informatics physician are essential in order to continue to provide this major surgery, which is essential for the patient's quality of life. A higher rating of this activity by the French health system is also necessary.

[A preliminary survey on the interest of eating probiotics, cypress and echinacea to prevent the apparition of winter infections]. / Enquête préliminaire sur l'intérêt de consommer des probiotiques, du cyprès et de l'échinacée en prévention des infections hivernales.

INTRODUCTION: Winter is a good time for viral. Some plants and probiotic strains could give a better protection to our organism by strengthening the immune system. OBJECTIVES: The objective of this preliminary survey was to evaluate the possible preventive effect against infections of Cupressus sempervirens/Echinacea purpurea combination (plants known for their immune and anti-viral effects) in association with probiotics during the winter season. METHODS: It's a declarative survey by questionnaire. The objective was to compare the occurrence of winter infections in two populations aged 18-65 years old in good health which used this complementation for at least 3 months period during winter period or not. RESULTS: The rate of incidence of flu (P = 0.012), common cold (P = 0.002) and throat infection (P = 0.0017) decreased in the group that took complementation compared to the group that didn't take complementation. The occurrence of colds was also significantly reduced in a subgroup of subjects that are more sensitive to infections during winter and took the complementation compared to the same subgroup of subjects that didn't take the complementation (36 vs 78% of colds, P = 0.004). CONCLUSIONS: The results show that consumption of both products for 3 months or more is associated to a lesser incidence of winter infections such as flu, cold and throat infection. It might be interesting to conduct a larger prospective study to determine the exact role of Lactibiane® and Phytostandard® of Cypressus-Echinacea in the prevention of these winter infections.

[Financial analysis of a department of general surgery in a French hospital. The new "fee-for-service" reimbursement system results in a high deficit for emergency care]. / Analyse comptable de l'activité d'un service de chirurgie digestive : l'activité d'urgence est fortement déficitaire. Quelles conséquences pour les patients ?

GOAL: The aim of this study was to perform a detailed analysis of income and expense in a department of general surgery in a French hospital under the new system of funding based on a "fee-for-service" principle. METHODS: All hospital stays of year 2006 were analysed retrospectively. The conditions of admission (elective vs. emergency), the principal diagnosis, and surgical procedures were examined. We determined hospital costs and the reimbursement for every admission. RESULTS: One thousand nine hundred and eighty-five hospitalizations generated an income of 8Meuros with a deficit of 1.3Meuros. The 775 elective admissions generated 50% of the income and 13% of the deficit (178,562euros). Seven hundred and forty-nine emergency admissions generated 45% of the income and 82% of deficit (1.1Meuros). Four hundred and sixty-one admissions for endoscopy generated 5% of the income and 5% of the deficit (67,249euros). Hospital stays of less than two days (the minimum duration of stay for total reimbursement) caused a loss of 122,624euros. Length of hospital stay below the lower limit caused a loss of 42,850euros. CONCLUSION: Elective surgical activity in digestive surgery can generate a balanced budget provided the length of hospital stay is reduced to the minimum, sometimes to the detriment of patient comfort. Emergency admissions result in a large deficit between cost and reimbursement; this fact may lead hospitals to avoid emergency activity in the future unless appropriate remedial measures are taken.

Induction of a melanoma-specific antibody response by a monovalent, but not a divalent, synthetic GM2 neoglycopeptide.

The GM2 ganglioside represents an important target for specific anticancer immunotherapy. We designed and synthesized a neoglycopeptide immunogen displaying one or two copies of the GM2 tetrasaccharidic moiety. These glycopeptides were prepared using the Huisgen cycloaddition, which enables the efficient ligation of the alkyne-functionalized biosynthesized GM2 with an azido CD4(+) T cell epitope peptide. It is worth noting that the GM2 can be produced on a gram scale in bacteria, which can be advantageous for a scale-up of the process. We show here for the first time that a fully synthetic glycopeptide, which is based on a ganglioside carbohydrate moiety, can induce human tumor cell-specific antibodies after immunization in mice. Interestingly, the monovalent, but not the divalent, form of GM2 peptide construct induced antimelanoma antibodies. Unlike traditional vaccines, this vaccine is a pure chemically-defined entity, a key quality for consistent studies and safe clinical evaluation. Therefore, such carbohydrate-peptide conjugate represents a promising cancer vaccine strategy for active immunotherapy targeting gangliosides.

[Complete heart block and myocardial ischaemia during a severe anaphylactic reaction]. / Bloc auriculoventriculaire complet peranesthésique et ischémie myocardique contemporains d'un choc anaphylactique grave.

An 83-year-old man had to be operated under general anaesthesia for a head skin tumor. The preanaesthetic exam of the cardiovascular function was reassuring but a cardiac arrest with a complete heart block occurred a few minutes after induction of anaesthesia. Resuscitation managing was successful but a myocardial ischaemia appeared. Biological tests confirmed severe anaphylactic reaction. The electrocardiographic expression, pathophysiology and management of cardiac anaphylaxis are discussed.

[Bradycardia induced by galantamine]. / Bradycardie liée à la galantamine.

An 80-year-old man had to be operated for cutaneous neoplasia. Local anaesthesia with sedation was required. Preoperative examination revealed a pronounced albeit asymptomatic bradycardia. Electrocardiogram showed a complete atrioventricular block. Use of a pacemaker was discussed. Finally, surgery was performed uneventfully after transient reversal of the anticholinesterasic effects of galantamine administered in Alzheimer's disease control over several hours with atropine.