Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety.

The inodilator levosimendan, in clinical use for over two decades, has been the subject of extensive clinical and experimental evaluation in various clinical settings beyond its principal indication in the management of acutely decompensated chronic heart failure. Critical care and emergency medicine applications for levosimendan have included postoperative settings, septic shock, and cardiogenic shock. As the experience in these areas continues to expand, an international task force of experts from 15 countries (Austria, Belgium, China, Croatia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Spain, Sweden, Switzerland, and the USA) reviewed and appraised the latest additions to the database of levosimendan use in critical care, considering all the clinical studies, meta-analyses, and guidelines published from September 2019 to November 2021. Overall, the authors of this opinion paper give levosimendan a "should be considered" recommendation in critical care and emergency medicine settings, with different levels of evidence in postoperative settings, septic shock, weaning from mechanical ventilation, weaning from veno-arterial extracorporeal membrane oxygenation, cardiogenic shock, and Takotsubo syndrome, in all cases when an inodilator is needed to restore acute severely reduced left or right ventricular ejection fraction and overall haemodynamic balance, and also in the presence of renal dysfunction/failure.

The role of age in post-cardiac arrest therapy in an elderly patient population.

AIM: We investigated the effect of age on post-cardiac arrest treatment outcomes in an elderly population, based on a local database and a systemic review of the literature. METHODS: Data were collected retrospectively from medical charts and reports. Sixty-one comatose patients, cooled to 32-34 °C for 24 h, were categorized into three groups: younger group (≤65 years), older group (66-75 years), and very old group (>75 years). Circumstances of cardiopulmonary resuscitation (CPR), patients' characteristics, post-resuscitation treatment, hemodynamic monitoring, neurologic outcome and survival were compared across age groups. Kruskal-Wallis test, Chi-square test and binary logistic regression (BLR) were applied. In addition, a literature search of PubMed/Medline database was performed to provide a background. RESULTS: Age was significantly associated with having a cardiac arrest on a monitor and a history of hypertension. No association was found between age and survival or neurologic outcome. Age did not affect hemodynamic parameter changes during target temperature management (TTM), except mean arterial pressure (MAP). Need of catecholamine administration was the highest among very old patients. During the literature review, seven papers were identified. Most studies had a retrospective design and investigated interventions and outcome, but lacked unified age categorization. All studies reported worse survival in the elderly, although old survivors showed a favorable neurologic outcome in most of the cases. CONCLUSION: There is no evidence to support the limitation of post-cardiac arrest therapy in the aging population. Furthermore, additional prospective studies are needed to investigate the characteristics and outcome of post-cardiac arrest therapy in this patient group.

Alkali Metal Cations Bonding to Carboxylate Anions: Studies using Mass Spectrometry and Quantum Chemical Calculations.

Data on the gas-phase energetics of anion/cation interactions are relatively scarce. In this work, gas-phase alkali metal cation basicity (AMCB) scales were established for a series of 15 benzoate ions XC6H4COO- with Li+, Na+, K+, Rb+, and Cs+ on the basis of mass spectrometry experiments and high-level calculations. A wide range of electron-donating and electron-withdrawing substituents were included in the study. The thermochemical values were calculated by ab initio methodologies and extrapolated to the complete basis set limit. For each metal cation, the experimental relative cation basicity values of the anions were established quantitatively by applying the Cooks' kinetic method to the cation-bound heterodimers [(XC6H4COO-)M+(YC6H4COO-)]-, generated by electrospray ionization. The self-consistency of these AMCB scales was ascertained by multiple overlap of the individual relative basicities. In parallel, the proton gas-phase basicities (GBs) of the benzoate anions (gas-phase acidities of the respective benzoic acids) were calculated in order to compare the results of the theoretical method with known experimental GB values. The experimental and calculated GB values agree quite accurately (average absolute deviation = 3.2 kJ mol-1). The relative experimental AMCB scales and the absolute calculated AMCB scales are highly correlated, and the two sets agree by better than 4 kJ mol-1. It is also demonstrated that the five series of calculated AMCBs are highly correlated with the calculated GB.

The association between the introduction of quantitative assessment of postpartum blood loss and institutional changes in clinical practice: an observational study.

BACKGROUND: Imprecise visual estimates of blood loss contribute to morbidity from postpartum hemorrhage. We examined the impact of quantitative assessment of postpartum blood loss on clinical practice and outcomes. METHODS: An observational study comparing blood loss, management and outcomes between two historical cohorts (August 2016 to January 2017 and August 2017 to January 2018) at an academic tertiary care center. Patients in the intervention group (second period) had blood loss quantified compared with visual estimation for controls. RESULTS: We included 7618 deliveries (intervention group n=3807; control group n=3811). There was an increase in the incidence of hemorrhage (blood loss >1 L) in the intervention group for both vaginal (2.2% vs 0.5%, P <0.001) and cesarean delivery (12.6% vs 6.4%, P <0.001). There was also a difference in median blood loss for vaginal (258 mL [151-384] vs 300 mL [300-350], P <0.001); and for cesarean delivery (702 mL [501-857] vs 800 mL [800-900], P <0.001). The median red blood cell units transfused was different in the intervention group having cesarean delivery (2 units [1-2] vs 2 units [2-2], P=0.043). Secondary uterotonic usage was greater in the intervention group for vaginal (22% vs 17.3%, P <0.001) but not cesarean delivery (7.0% vs 6.0%, P=0.177). Laboratory costs were different, but not the re-admission rate or length of stay. CONCLUSIONS: Quantifying blood loss may result in increased vigilance for vaginal and cesarean delivery. We identified an association between quantifying blood loss and improved identification of postpartum hemorrhage, patient management steps and cost savings.

Role of supracricoid partial laryngectomy with cricohyoidoepiglottopexy in glottic carcinoma with anterior commissure involvement.

OBJECTIVES: To analyze oncologic and functional outcomes after supracricoid laryngectomy with cricohyoidoepiglottopexy (SCL-CHEP) in glottic carcinoma with anterior commissure (AC) involvement, to determine predictive factors, and to compare results with those reported for other therapeutic strategies. MATERIAL AND METHODS: A retrospective analysis included all patients who underwent SCL-CHEP for glottic squamous cell carcinoma with anterior commissure involvement in our institution, between 2000 and 2014. Swallowing function was evaluated on the DOSS (Dysphagia Outcomes and Severity Scale). RESULTS: Fifty-three patients were included. Three-year overall, cause-specific and recurrence-free survival rates were 86, 95 and 80%, respectively. There were 5 cases of local recurrence (9%), all treated by total laryngectomy. Smoking was the only predictive factor of recurrence-free survival (P=0.02). Mean DOSS score was 5.5±0.9. DOSS scores≥6 (normal oral feeding) were recovered by 59% of patients. T-stage≥2 was the only predictive factor for DOSS score (P=0.04). CONCLUSION: In glottic carcinoma with anterior commissure involvement, SCL with CHEP provided a local control rate of more than 90%, which is higher than reported with endoscopic surgery or external radiotherapy. However, contrary to LSC, salvage of local recurrence can often be obtained by conservative treatments after endoscopic surgery. Therefore, total-laryngectomy-free survival rates after SCL-CHEP and endoscopic surgery are finally comparable.

[Value of procalcitonin for infants with bronchiolitis in an emergency department]. / Dosage de la procalcitonine et bronchiolites vues dans un service d'accueil des urgences pédiatriques.

CONTEXT: Very few studies have evaluated the role of procalcitonin (PCT) in infants with bronchiolitis. AIMS: To describe infants who had both a diagnosis of bronchiolitis at the emergency department and a blood test including PCT, and to compare the characteristics of children according to the PCT value. METHODS: Infants admitted to the Pediatric Emergency Department between 1 January 2014 and 31 December 2014 who had a diagnosis of bronchiolitis and a blood test including PCT were included. The clinical, biological, and radiological characteristics of the infants with PCT <1 or ≥1g/L were compared. RESULTS: One hundred thirty six infants were included. Patients with high PCT (n=20) had a higher temperature (38.5°C, IQR=37.8-38.6 vs. 37.5°C, IQR=37.1-38.2; P<0.01), C-reactive protein (50mg/L, IQR=25-83 vs. 5mg/L, IQR=0-19; P<0.01), and neutrophils (7.8×109/L, IQR=6.0-8.5 vs 4.5×109/L, IQR=2.9-6.6; P<0.01) higher than patients with low PCT (n=116). Presence on the chest x-ray of alveolar condensation did not differ between the two PCT groups. Infants coming from the low-PCT group received fewer antibiotics (14.7% vs 65%; P<0.01). CONCLUSION: In a Pediatric Emergency Department, PCT with a value of 1 or more cannot predict the presence of alveolar condensation on the chest x-ray. It seems to be associated with the antibiotics prescription, even if this could not be proved because of the design of the study.

The medial pterygoid muscle: a stabiliser of horizontal jaw movement.

There is limited information of the normal function of the human medial pterygoid muscle (MPt). The aims were to determine whether (i) the MPt is active throughout horizontal jaw movements with the teeth apart and (ii) whether single motor units (SMUs) are active during horizontal and opening-closing jaw movements. Intramuscular electrodes were placed in the right MPt of 18 participants who performed five teeth-apart tasks: (i) postural position, (ii) ipsilateral (i.e. right) jaw movement, (iii) contralateral movement, (iv) protrusive movement and (v) opening-closing movement. Movement tasks were guided by a target and were divided into BEFORE, OUT, HOLDING, RETURN and AFTER phases according to the movement trajectories recorded by a jaw tracking system. Increased EMG activity was consistently found in the OUT, HOLDING and RETURN phases of the contralateral and protrusive movement tasks. An increased RETURN phase activity in the ipsilateral task indicates an important role for the MPt in the contralateral force vector. Of the 14 SMUs active in the opening-closing task, 64% were also active in at least one horizontal task. There were tonically active SMUs at the postural jaw position in 44% of participants. These new data point to an important role for the MPt in the fine control of low forces as required for stabilisation of vertical mandibular position not only to maintain postural position, but also throughout horizontal jaw movements with the teeth apart. These findings provide baseline information for future investigations of the possible role of this muscle in oro-facial pain conditions.

Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.

BACKGROUND: Pembrolizumab and nivolumab are immune checkpoint inhibitors targeting PD-1 that have recently been approved in pretreated recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. In the clinic, some patients seem not only not to benefit from anti-PD-L1/PD-1 agents but rather to experience an acceleration of tumor growth kinetics (TGK). PATIENTS AND METHODS: We retrospectively compared TGK on immunotherapy and TGK on last treatment in patients with R/M HNSCC treated with PD-1/PD-L1 inhibitors in four French centers. The TGK ratio (TGKR, ratio of the slope of tumor growth before treatment and the slope of tumor growth on treatment) was calculated. Hyperprogression was defined as a TGKR ≥ 2. RESULTS: From September 2012 to September 2015, 34 patients were identified. Patterns of recurrence included exclusive loco-regional recurrence in 14 patients, exclusive distant metastases in 11 patients, and both in 9 patients. No pseudo-progression was observed. Hyperprogression was observed in 10 patients (29%), including 9 patients with at least a locoregional recurrence, and only 1 patient with exclusively distant metastases. Hyperprogression significantly correlated with a regional recurrence (TGKR ≥ 2: 90% versus TGKR < 2: 37%, P = 0.008), but not with local or distant recurrence. Hyperprogression was associated with a shorter progression-free survival (PFS) according to RECIST (P = 0.003) and irRECIST (P = 0.02), but not with overall survival (P = 0.77). CONCLUSIONS: Hyperprogression was observed in 29% of patients with R/M HNSCC treated with anti-PD-L1/PD-1 agents and correlated with a shorter PFS. It occurred in 39% of patients with at least a locoregional recurrence and 9% of patients with exclusively distant metastases. No pseudo-progressions were reported. Mechanisms and causality of hyperprogression should further be assessed through prospective controlled studies.

Effect of experimental anterior temporalis muscle pain on jaw movements.

To test the hypotheses that experimental noxious stimulation of the anterior temporalis muscle results in significant decreases in jaw movement amplitude and velocity, and there are significant correlations between scores of mood or pain-related cognitions and amplitude and velocity. The jaw movements of 14 asymptomatic participants were recorded during standardised open/close jaw movements and free and standardised chewing tasks. Tonic infusion of hypertonic saline into the right anterior temporalis muscle maintained pain intensity between 40 and 60 mm on a 100-mm visual analogue scale. Tasks were performed in a single session in the following sequence: baseline condition, test 1 condition (during hypertonic or isotonic saline infusion), test 2 condition (during saline infusion) (10-min rest between conditions). Participants completed the Depression, Anxiety and Stress Scale (DASS-21) and the Pain Catastrophizing Scale (PCS). Amplitude and velocity of opening and closing were compared between conditions with a repeated-measures analysis of variance (anova), and Spearman's rank correlation coefficient explored correlations; statistical significance: P < 0·05. For any of the three tasks, there were no significant differences in kinematic variables between any condition and no significant correlations between DASS-21 or PCS scores and kinematic variables during hypertonic saline infusion. The absence of a significant reduction in velocity or amplitude of open/close or chewing jaw movements during experimental temporalis muscle pain is not consistent with the Pain Adaptation Model proposing decreases in kinematic measures in pain. The lack of significant correlations between psychological variables and measures of jaw movement may reflect the low scores reported by our study sample.

Source identification and distribution reveals the potential of the geochemical Antarctic sea ice proxy IPSO25.

The presence of a di-unsaturated highly branched isoprenoid (HBI) lipid biomarker (diene II) in Southern Ocean sediments has previously been proposed as a proxy measure of palaeo Antarctic sea ice. Here we show that a source of diene II is the sympagic diatom Berkeleya adeliensis Medlin. Furthermore, the propensity for B. adeliensis to flourish in platelet ice is reflected by an offshore downward gradient in diene II concentration in >100 surface sediments from Antarctic coastal and near-coastal environments. Since platelet ice formation is strongly associated with super-cooled freshwater inflow, we further hypothesize that sedimentary diene II provides a potentially sensitive proxy indicator of landfast sea ice influenced by meltwater discharge from nearby glaciers and ice shelves, and re-examination of some previous diene II downcore records supports this hypothesis. The term IPSO25-Ice Proxy for the Southern Ocean with 25 carbon atoms-is proposed as a proxy name for diene II.

[Management and clinical outcome in patients over 80 years with rectal cancer treated between 2006 and 2008 in Southern France (PACA region)]. / Prise en charge et devenir des patients de plus de 80ans atteints d'un cancer du rectum, en région Provence-Alpes-Côte-d'Azur de 2006 à 2008.

PURPOSE: Rectal cancer is increasingly prevalent in elderly patients. Their clinical history and outcome after treatment are poorly described. This retrospective study was undertaken to provide more data and to compare therapeutic strategies to the standard of care for younger patients. PATIENTS AND METHODS: Patients concerned were aged 80 years or older, with a rectal cancer diagnosed between 2006 and 2008 and treated in Provence-Alpes-Côte-d'Azur (PACA), irrespective of stage and treatment of the disease. Overall survival and relapse-free-survival were correlated with patients' characteristics and treatment. The adopted therapeutic strategy was then compared to the standard-of-care for younger patients. RESULTS: With a median follow-up of 36 months, among the 160 patients included, the 3-year overall survival and relapse-free survival were 59.2% and 76.6%, respectively for the 117 patients who received a treatment with curative intent. In the multivariate analysis, node status and surgery independently influenced overall survival, while relapse-free survival was influenced by age, N status, and gender. For T0-T2 tumours, patients were treated similarly to younger patients with an overall survival of 83.6% and a relapse-free survival of 95.2%. For T3-T4 tumours, the 3-year relapse-free survival was 65%, even with a less aggressive strategy. CONCLUSION: Surgical resection after evaluation using the Comprehensive Geriatric Assessment (CGA) test should be the standard treatment for localized rectal cancer (T0-T2) in elderly patients, as it is in younger patients. For locally advanced lesions (T3-T4), results obtained after a conservative approach suggest that a non-surgical strategy can be used in elderly patients.

[Salvage HIFU after radiotherapy and salvage radiotherapy after HIFU in locally recurrent prostate cancer: Retrospective analysis of morbidity]. / Traitements de rattrapage par HIFU après radiothérapie première et par radiothérapie après HIFU première dans la récidive locale du cancer de prostate: analyse rétrospective de la toxicité

OBJECTIVES: To evaluate the toxicity of therapeutic sequences High Intensity Focused Ultrasound (HIFU)-salvage radiotherapy (HIFU-RT) or radiotherapy-salvage HIFU (RT-HIFU) in case of locally recurrent prostate cancer. MATERIALS AND METHODS: Nineteen patients had a local recurrence of prostate cancer. Among them, 10 patients were treated by HIFU-RT and 9 patients by RT- HIFU (4 by external beam radiotherapy [EBR] and 5 by brachytherapy [BRACHY]). Urinary side effects were assessed using CTCAE v4. RESULTS: At the time of the initial management, the median age was 66.5 years (53-72), the median PSA was 10.8ng/mL (3.4-50) and the median initial Gleason score was 6.3 (5-8). Median follow-up after salvage treatment was 46.3 months (2-108). Thirty percent of the patients in the HIFU-RT group and 33.3 % of the patients in the RT-HIFU group, all belonging to the sub-group BRACHY-HIFU, had urinary complication greater than or equal to grade 2. Among all the patients, only 1 had grade 1 gastrointestinal toxicity. CONCLUSION: BRACHY-HIFU sequence seems to be purveyor of many significant urinary side effects. A larger database is needed to confirm this conclusion.

[Prostate cancer boost using high-dose-rate brachytherapy: impact of the learning curve on the dosimetry]. / Curiethérapie de haut débit de dose après radiothérapie externe d'un cancer de prostate : impact de la courbe d'apprentissage sur la dosimétrie.

PURPOSE: To analyse the influence of the learning curve on dosimetric data for high-dose-rate brachytherapy prostate cancer boost. PATIENTS AND METHODS: From February 2009 to May 2012, after a first course of external beam radiation therapy (46Gy/23 fractions), 124 patients underwent high-dose-rate brachytherapy boost using Plato™ (Nucletron, an Elekta company, Elekta AB, Stockholm, Sweden). The impact of the learning curve on the dosimetric quality of the prostate implant was assessed. The dosimetric data have been analysed: clinical target volume (CTV), D90 (dose to 90 % of CTV), D100, V100 (part on the CTV receiving 100 % of the dose), V150, V200 and DHI (dose non-homogeneity index). The doses delivered to 0.1, 1 and 2 cm(3) of the rectum and urethra were calculated. RESULTS: During the study period (39 months), a significant reduction of V150 (P<0.001), V200 (P<0.001), D0.1rectum (P<0.001), D1rectum (P<0.001), D2rectum (P<0.001), D0.1urethra (P<0.001), and D1urethra (P<0.002) was observed associated with a significant degradation of the D90 (P<0.001) but not significant for the V100 (P=0.29) and the D100 (P=0.3). CONCLUSION: This study confirms that the dosimetric quality of high-dose-rate brachytherapy prostate implant is significantly improved during the learning curve period.

Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome.

BACKGROUND: (18)Fluor-deoxy-glucose PET-scanning of glycolytic metabolism is being used for staging in many tumors however its impact on prognosis has never been studied in breast cancer. METHODS: Glycolytic and hypoxic markers: glucose transporter (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 and 4 (MCT1, 4), MCT accessory protein basigin and lactate-dehydrogenase A (LDH-A) were assessed by immunohistochemistry in two cohorts of breast cancer comprising 643 node-negative and 127 triple negative breast cancers (TNBC) respectively. RESULTS: In the 643 node-negative breast tumor cohort with a median follow-up of 124 months, TNBC were the most glycolytic (≈70%), followed by Her-2 (≈50%) and RH-positive cancers (≈30%). Tumoral MCT4 staining (without stromal staining) was a strong independent prognostic factor for metastasis-free survival (HR=0.47, P=0.02) and overall-survival (HR=0.38, P=0.002). These results were confirmed in the independent cohort of 127 cancer patients. CONCLUSION: Glycolytic markers are expressed in all breast tumors with highest expression occurring in TNBC. MCT4, the hypoxia-inducible lactate/H(+) symporter demonstrated the strongest deleterious impact on survival. We propose that MCT4 serves as a new prognostic factor in node-negative breast cancer and can perhaps act soon as a theranostic factor considering the current pharmacological development of MCT4 inhibitors.

Needle-related ultrasound artifacts and their importance in anaesthetic practice.

Real-time ultrasound guidance for any intervention relies on visualization of needle advancement towards a target. Unfortunately, correct identification of the needle tip is not straightforward, as artifacts always distort the image. The ultrasonic appearance of the needle is often degraded by reverberation, comet tail, side-lobe, beam-width, or bayonet artifacts, which can easily confuse an unprepared operator. Furthermore, the typical needle image, that is, a dot or a straight line (out-of-plane and in-plane approaches, respectively), is also a result of artifacts that hide the real dimensions of the needle. Knowledge and correct interpretation of these artifacts is important for safe practice and is paramount to success when precise needle manipulation is mandatory, for example, when the target is small. In this review, authors discuss the most important needle-related artifacts and provide a physical explanation focusing on implications for everyday practice. Recent advances that allow increased needle visualization and reduction of artifacts are also discussed.

[Vaccination coverage against influenza and pneumococcus for patients admitted to a pulmonary care service]. / Couverture vaccinale grippale et pneumococcique dans un SSR de pneumologie.

INTRODUCTION: The aim of this work was to study the vaccination coverage against influenza and pneumococcus in patients admitted to a pulmonary care department. METHODS: Between September 2010 and August 2011, we conducted a prospective observational study of patients admitted to our institution. A history of vaccination against influenza and pneumococcus was sought systematically using a standardized questionnaire. RESULTS: Of 476 patients admitted to the pulmonary service at our institution, 246 had COPD, 175 had undergone thoracic surgery and 55 had a chronic respiratory disease other than COPD. The average age of our patients was 67 years (60-76) and the sex-ratio was 1.6 (291M and 185 F). Amongst the target population for influenza vaccination, coverage was 73%. The main reason for patients not to have been vaccinated against influenza was patient refusal or intolerance (59%). Amongst the target population for antipneumococcal vaccination, the coverage was 53%. The main reason for the lack of vaccination against pneumococcus was that no offer of vaccination had been made by a physician (92.5%). CONCLUSION: Vaccination coverage was low, in particular for pneumococcus. Pulmonary departments are strategic sites which could take action to systematically improve vaccination coverage.

Management and clinical outcome of rectal cancer in patients ≥ 80 years treated in southern France (PACA region) between 2006 and 2008.

BACKGROUND: Rectal cancer is increasingly prevalent in the elderly patients. Their clinical history and outcome after treatment are poorly described. This retrospective study was undertaken to provide more data and to compare therapeutic strategies to the standard of care for younger patients. PATIENTS AND METHODS: Data were retrospectively provided by gastroenterologists, oncologists, and gerontologists of Provence-Alpes-Côte-d'Azur (PACA). Patients concerned were aged 80 years or older, with a rectal cancer diagnosed between 2006 and 2008, irrespective of stage and (the) treatment of the disease. Overall survival (OS) and relapse-free-survival (RFS) were correlated with patient characteristics and treatment. The adopted therapeutic strategy was then compared to the standard-of-care for younger patients. RESULTS: Median follow-up was 36 months. The 3-year OS was 47.4% for the 160 patients analyzed, and 59.2% for the 117 patients treated with curative intent. The 3-year RFS was 76.6% in the "curative" population. In the multivariate analysis, node status and surgery independently influenced OS, while RFS was influenced by age, N status, and gender. For T0-T2 tumors, patients were treated similar to younger patients with an OS of 83.6% and a RFS of 95.2%, respectively. For T3-T4 tumors, 3-year RFS was 65%, even with a less aggressive strategy. CONCLUSION: Surgical resection after evaluation using Comprehensive Geriatric Assessment (CGA) should be the standard treatment for localized rectal cancer (T0-T2) in elderly patients, as it is in younger patients. For locally advanced lesions (T3-T4), results obtained after a conservative approach suggest that a non-surgical strategy can be used in elderly patients.

Differential gene body methylation and reduced expression of cell adhesion and neurotransmitter receptor genes in adverse maternal environment.

Early life adversity, including adverse gestational and postpartum maternal environment, is a contributing factor in the development of autism, attention deficit hyperactivity disorder (ADHD), anxiety and depression but little is known about the underlying molecular mechanism. In a model of gestational maternal adversity that leads to innate anxiety, increased stress reactivity and impaired vocal communication in the offspring, we asked if a specific DNA methylation signature is associated with the emergence of the behavioral phenotype. Genome-wide DNA methylation analyses identified 2.3% of CpGs as differentially methylated (that is, differentially methylated sites, DMSs) by the adverse environment in ventral-hippocampal granule cells, neurons that can be linked to the anxiety phenotype. DMSs were typically clustered and these clusters were preferentially located at gene bodies. Although CpGs are typically either highly methylated or unmethylated, DMSs had an intermediate (20-80%) methylation level that may contribute to their sensitivity to environmental adversity. The adverse maternal environment resulted in either hyper or hypomethylation at DMSs. Clusters of DMSs were enriched in genes that encode cell adhesion molecules and neurotransmitter receptors; some of which were also downregulated, indicating multiple functional deficits at the synapse in adversity. Pharmacological and genetic evidence links many of these genes to anxiety.

Iodine status has no impact on thyroid function in early healthy pregnancy.

Aim. To assess the impact of iodine status in early pregnancy on thyroid function. Methods. Women >18 years old seen at their first prenatal consult before 12 weeks of amenorrhea and without personal thyroid history were proposed thyroid screening and were eligible if they had strictly normal thyroid tests (fT4 > 10th percentile, TSH < 2.5 mUI/L, negative anti-TPO antibodies). Evaluation included thyroid ultrasound, extensive thyroid tests, and ioduria (UIE). Results. 110 women (27.5 y, 8 weeks of amenorrhea, smoking status: 28% current smokers) were enrolled. Results are expressed as medians. UIE was 116 µg/L. 66.3% of women had iodine deficiency (ID) defined as UIE < 150. FT4 was 14.35 pmol/L; TSH 1.18 mUI/L; fT3 5 pmol/L; thyroglobulin 17.4 ng/mL; rT3 0.27 ng/mL; thyroid volume: 9.4 ml. UIE did not correlate with any thyroid tests, but correlated negatively with thyroid volume. UIE and all thyroid tests, except fT3, correlated strongly with ßhCG. Smoking correlated with higher thyroid volume and thyroglobulin and with lower rT3. Conclusions. In pregnant women selected for normal thyroid function, mild ID is present in 66% during the 1st trimester. The absence of correlation between UIE and thyroid tests at that stage contrasts with the impact of ßhCG and, to a lesser degree, maternal smoking.