A large West Antarctic Ice Sheet explains early Neogene sea-level amplitude.

Early to Middle Miocene sea-level oscillations of approximately 40-60 m estimated from far-field records1-3 are interpreted to reflect the loss of virtually all East Antarctic ice during peak warmth2. This contrasts with ice-sheet model experiments suggesting most terrestrial ice in East Antarctica was retained even during the warmest intervals of the Middle Miocene4,5. Data and model outputs can be reconciled if a large West Antarctic Ice Sheet (WAIS) existed and expanded across most of the outer continental shelf during the Early Miocene, accounting for maximum ice-sheet volumes. Here we provide the earliest geological evidence proving large WAIS expansions occurred during the Early Miocene (~17.72-17.40 Ma). Geochemical and petrographic data show glacimarine sediments recovered at International Ocean Discovery Program (IODP) Site U1521 in the central Ross Sea derive from West Antarctica, requiring the presence of a WAIS covering most of the Ross Sea continental shelf. Seismic, lithological and palynological data reveal the intermittent proximity of grounded ice to Site U1521. The erosion rate calculated from this sediment package greatly exceeds the long-term mean, implying rapid erosion of West Antarctica. This interval therefore captures a key step in the genesis of a marine-based WAIS and a tipping point in Antarctic ice-sheet evolution.

The amplitude and origin of sea-level variability during the Pliocene epoch.

Earth is heading towards a climate that last existed more than three million years ago (Ma) during the 'mid-Pliocene warm period'1, when atmospheric carbon dioxide concentrations were about 400 parts per million, global sea level oscillated in response to orbital forcing2,3 and peak global-mean sea level (GMSL) may have reached about 20 metres above the present-day value4,5. For sea-level rise of this magnitude, extensive retreat or collapse of the Greenland, West Antarctic and marine-based sectors of the East Antarctic ice sheets is required. Yet the relative amplitude of sea-level variations within glacial-interglacial cycles remains poorly constrained. To address this, we calibrate a theoretical relationship between modern sediment transport by waves and water depth, and then apply the technique to grain size in a continuous 800-metre-thick Pliocene sequence of shallow-marine sediments from Whanganui Basin, New Zealand. Water-depth variations obtained in this way, after corrections for tectonic subsidence, yield cyclic relative sea-level (RSL) variations. Here we show that sea level varied on average by 13 ± 5 metres over glacial-interglacial cycles during the middle-to-late Pliocene (about 3.3-2.5 Ma). The resulting record is independent of the global ice volume proxy3 (as derived from the deep-ocean oxygen isotope record) and sea-level cycles are in phase with 20-thousand-year (kyr) periodic changes in insolation over Antarctica, paced by eccentricity-modulated orbital precession6 between 3.3 and 2.7 Ma. Thereafter, sea-level fluctuations are paced by the 41-kyr period of cycles in Earth's axial tilt as ice sheets stabilize on Antarctica and intensify in the Northern Hemisphere3,6. Strictly, we provide the amplitude of RSL change, rather than absolute GMSL change. However, simulations of RSL change based on glacio-isostatic adjustment show that our record approximates eustatic sea level, defined here as GMSL unregistered to the centre of the Earth. Nonetheless, under conservative assumptions, our estimates limit maximum Pliocene sea-level rise to less than 25 metres and provide new constraints on polar ice-volume variability under the climate conditions predicted for this century.

[Transition, fertility and options for preservation of fertility]. / Transition, fertilité et options de préservation de fertilité.

Oftentimes ignored or infrequently expressed, some transgender persons harbor a desire for parenthood. Given the evolution of medical techniques and the enacting of legislative reforms, it is henceforth possible to propose fertility preservation strategies in the overall context of gender transidentity. During the "female to male" (FtM) transition pathway, androgen therapy has an impact on gonadic function, generally inducing blockage of the ovarian function, with amenorrhea. Even though these events may be reversed on cessation of treatment, the possible long-term effects on future fertility and on the health of children yet to be born are little known. Moreover, transition surgeries definitively compromise the possibility of pregnancy insofar as they involve bilateral adnexectomy and/or hysterectomy. Options for fertility preservation in the framework of FtM transition are premised on cryopreservation of oocytes and/or ovarian tissue. In a comparable manner, even though relevant documentation is lacking, hormonal treatments for persons transitioning from male to female (MtF) can have an impact on future fertility. In the event of surgery involving bilateral orchidectomy in which spermatozoid cryopreservation has not been carried out, fertility is definitively impossible. In both cases and under present-day legislation, numerous legal and regulatory barriers render highly problematic the reutilization of cryopreserved gametes. Given these different constraints, it is indispensable to closely supervise these types of treatment by proposing psychological support.

Eating context and ultraprocessed food consumption among UK adolescents.

We aimed to evaluate the association between eating context patterns and ultraprocessed food consumption at two main meal occasions in a representative sample of UK adolescents. Data were acquired from 4-d food records of adolescents aged 11-18 years, who participated in the 2014-2016 UK National Diet and Nutrition Survey (n 542). The eating context was assessed considering the location of the meal (lunch and dinner) occasion, the individuals present, whether the television was on and if the food was consumed at a table. Ultraprocessed foods were identified using the NOVA classification. Exploratory factor analysis was used to identify eating context patterns for lunch and dinner. Linear regression models adjusted for the covariates were utilised to test the association between eating context patterns and the proportion of total daily energy intake derived from ultraprocessed foods. Their contribution was about 67 % to energy intake. Three patterns were retained for lunch ('At school with friends', 'TV during family meal' and 'Out-of-home (no school)'), and three patterns were retained for dinner ('Watching TV alone in the bedroom', 'TV during family meal' and 'Out-of-home with friends'). At lunch, there was no significant association between any of the three patterns and ultraprocessed food consumption. At dinner, the patterns 'Watching TV alone in the bedroom' (coefficient: 4·95; 95 % CI 1·87, 8·03) and 'Out-of-home with friends' (coefficient: 3·13; 95 % CI 0·21, 6·14) were associated with higher consumption of ultraprocessed food. Our findings suggest a potential relationship between the immediate eating context and ultraprocessed food consumption by UK adolescents.

Potential reductions in ultra-processed food consumption substantially improve population cardiometabolic-related dietary nutrient profiles in eight countries.

BACKGROUND AND AIMS: The negative effect on dietary nutrient profiles is the most obvious mechanism explaining the higher risk of cardiometabolic diseases associated with increased dietary share of UPF observed in large cohort studies. We estimate the proportion of diets with excessive energy density, excessive free sugars or saturated fat contents and insufficient fiber that could be avoided, if UPF consumption was reduced to levels among lowest consumers across eight countries, as well as the proportion of diets with multiple inadequacies. METHODS AND RESULTS: Using nationally-representative cross-sectional surveys from Brazil (2008-09), Chile (2010), Colombia (2005), Mexico (2012), Australia (2011-12), the UK (2008-16), Canada (2015), and the US (2015-16), inadequate energy density (≥2.25 kcal/g) or contents of free sugars (>10% of total energy intake), saturated fats (>10% of total energy intake) and fiber (<25 g/2000 kcal) population attributable fractions were quantified. Substantial reductions in nutrient inadequacies would be observed ranging from 50.4% in Chile to 76.8% in US for dietary energy density, from 15.5% in Colombia to 68.4% in Australia for free sugars, from 9.5% in Canada to 35.0% in Mexico for saturated fats, and from 10.3% in UK to 37.9% in Mexico for fiber. Higher reductions would be observed for diets with multiple nutrient inadequacies: from 27.3% in UK to 77.7% in Australia for ≥3 and from 69.4% in Canada to 92.1% in US, for 4 inadequacies. CONCLUSIONS: Lowering dietary contribution of UPF to levels among country-specific lowest consumers is a way to improve population cardiometabolic-related dietary nutrient profiles.

High-clearance anti-amyloid immunotherapies in Alzheimer's disease. Part 2: putative scenarios and timeline in case of approval, recommendations for use, implementation, and ethical considerations in France.

In 2021, aducanumab, an immunotherapy targeting amyloid-ß, was approved for Alzheimer's disease (AD) by the US Food and Drug Administration thanks to positive results on a putative biological surrogate marker. This approval has raised an unprecedented controversy. It was followed by a refusal of the European Medicine Agency, which does not allow the marketing of drugs solely on biological arguments and raised safety issues, and important US coverage limitations by the Centers for Medicare & Medicaid Services. Two other anti-amyloid immunotherapies showed significant results regarding a clinical outcome in phase II trials, and five drugs are being studied in phase III trials. Lecanemab is currently under examination for an 'Accelerated Approval' in the US, with an expected decision in January 2023. The common feature and novelty of these anti-amyloid immunotherapies, compared to those tested in previous trials of the 2010s, is their ability to induce a high clearance of amyloid load, as measured with positron emission tomography, in the brain of early-stage biomarker-proven AD patients. In the first part of this review, we underlined through a meta-analysis that the pooled data from high-clearance anti-amyloid immunotherapies trials demonstrated a significant but slight clinical effect after 18 months. Still, safety remains an issue with serious and symptomatic amyloid-related imaging abnormalities, which are seldom (∼1 per 200 treated patients) but occur beyond chance. In the second part of this review, we hypothesized that there is a high probability that some phase III trials of high-clearance anti-amyloid immunotherapies in early AD will finally be unarguably positive on clinical outcomes in the next five years with acceptable safety data. This may, in turn, lead to approval by the European Medicine Agency if the risk-benefit profile is deemed favorable. Such approval would be a game-changer in managing AD patients and for the organization of memory clinics in France. We review the possible timeline and scenarios for putative approval in France and make propositions regarding putative use in clinical practice, putative implementation in a real-life setting, and ethical considerations.

High-clearance anti-amyloid immunotherapies in Alzheimer's disease. Part 1: Meta-analysis and review of efficacy and safety data, and medico-economical aspects.

In 2021, aducanumab, an immunotherapy targeting amyloid-ß, was approved for Alzheimer's disease (AD) by the US Food and Drug Administration thanks to positive results on a putative biological surrogate marker. This approval has raised an unprecedented controversy. It was followed by a refusal of the European Medicine Agency, which does not allow the marketing of drugs solely on biological arguments and raised safety issues, and important US coverage limitations by the Centers for Medicare & Medicaid Services. Two other anti-amyloid immunotherapies showed significant results regarding a clinical outcome in phase 2 trials, and five drugs are being studied in phase 3 trials. Compared to those tested in previous trials of the 2010s, the common feature and novelty of these anti-amyloid immunotherapies is their ability to induce a high clearance of amyloid load, as measured with positron emission tomography, in the brain of early-stage biomarker-proven AD patients. Here, we review the available evidence regarding efficacy and safety data and medico-economical aspects for high-clearance anti-amyloid immunotherapies. We also perform frequentist and Bayesian meta-analyses of the clinical efficacy and safety of the highest dose groups from the two aducanumab phase 3 trials and the donanemab and lecanemab phase 2 trials. When pooled together, the data from high-clearance anti-amyloid immunotherapies trials confirm a statistically significant clinical effect of these drugs on cognitive decline after 18 months (difference in cognitive decline measured with CDR-SB after 18 months between the high dose immunotherapy groups vs. placebo = -0.24 points; P=0.04, frequentist random-effect model), with results on ADAS-Cog being the most statistically robust. However, this effect remains below the previously established minimal clinically relevant values. In parallel, the drugs significantly increased the occurrence of amyloid-related imaging abnormalities-edema (ARIA-E: risk ratio=13.39; P<0.0001), ARIA-hemorrhage (risk ratio=2.78; P=0.0002), and symptomatic and serious ARIA (7/1321=0.53% in the high dose groups versus 0/1446 in the placebo groups; risk ratio=6.44; P=0.04). The risk/benefit ratio of high-clearance immunotherapies in early AD is so far questionable after 18 months. Identifying subgroups of better responders, the perspective of combination therapies, and a longer follow-up may help improve their clinical relevance. Finally, the preliminary evidence from medico-economical analyses seems to indicate that the current cost of aducanumab in the US is not in reasonable alignment with its clinical benefits.

The multi-millennial Antarctic commitment to future sea-level rise.

Atmospheric warming is projected to increase global mean surface temperatures by 0.3 to 4.8 degrees Celsius above pre-industrial values by the end of this century. If anthropogenic emissions continue unchecked, the warming increase may reach 8-10 degrees Celsius by 2300 (ref. 2). The contribution that large ice sheets will make to sea-level rise under such warming scenarios is difficult to quantify because the equilibrium-response timescale of ice sheets is longer than those of the atmosphere or ocean. Here we use a coupled ice-sheet/ice-shelf model to show that if atmospheric warming exceeds 1.5 to 2 degrees Celsius above present, collapse of the major Antarctic ice shelves triggers a centennial- to millennial-scale response of the Antarctic ice sheet in which enhanced viscous flow produces a long-term commitment (an unstoppable contribution) to sea-level rise. Our simulations represent the response of the present-day Antarctic ice-sheet system to the oceanic and climatic changes of four representative concentration pathways (RCPs) from the Fifth Assessment Report of the Intergovernmental Panel on Climate Change. We find that substantial Antarctic ice loss can be prevented only by limiting greenhouse gas emissions to RCP 2.6 levels. Higher-emissions scenarios lead to ice loss from Antarctic that will raise sea level by 0.6-3 metres by the year 2300. Our results imply that greenhouse gas emissions in the next few decades will strongly influence the long-term contribution of the Antarctic ice sheet to global sea level.

Risk and protective behaviors for chronic non-communicable diseases among Brazilian adults.

OBJECTIVES: This study aimed to analyze behavioral patterns of protective and risk factors for chronic non-communicable diseases (NCDs) among adults and to explore the association between these patterns and sociodemographic characteristics using data from the National Health Survey 2013. STUDY DESIGN: This was a cross-sectional study. METHODS: This is a population-based study, nationwide, of individuals aged ≥18 years (n = 60,202). The sampling process used was grouping with three selection stages: census sector, households, and individuals. The factor analysis by principal component was used to identify behavioral patterns of protective and risk factors for NCDs. Linear regression was used to explore the association between patterns and sociodemographic characteristics. RESULTS: Two behavioral patterns were identified: a 'protective pattern' featured by consumption of vegetable, fruits/natural fruit juice, and low-fat milk and recommended physical activity practice during leisure time; and a 'risk pattern' characterized by consumption of high-fat meat and soft drinks, alcohol abuse, and smoking habit. Adherence to the protective pattern was associated with older White women who had higher levels of education, were economically active, and lived in the urban areas of the country. Younger, economically active men living in the urban areas were associated with the risk patterns. CONCLUSIONS: Two behavioral patterns for NCDs have been identified and are distributed non-randomly in the adult Brazilian population. These findings are expected to contribute to better targeting health promotion and prevention of NCDs.

Conjunctival Lymphoma With Nasal Spread Through the Nasolacrimal Duct.

Conjunctival mucosa-associated lymphoid tissue lymphoma classically presents as a subconjunctival mass, most often in the fornix. The presence of conjunctival mucosa-associated lymphoid tissue lymphoma with spread down the nasolacrimal duct has only been reported once previously. The authors present a case of a 35-year-old woman with a right conjunctival mass in the inferior fornix along with sinus congestion and fullness. A biopsy of the conjunctival mass and the nasal turbinate revealed a conjunctival mucosa-associated lymphoid tissue lymphoma. Therefore, it is important to consider spread down the nasolacrimal duct in patients with conjunctival lymphoma also presenting with difficulty breathing or nasal congestion.

Change in Lower Eyelid Contour Following Ectropion Repair With Lateral Tarsal Strip.

PURPOSE: To evaluate the change in lateral canthal angle (LCA), inferior ocular surface exposed (IOSE), lower eyelid curvature, and margin-to-reflex distance 2 in those undergoing lower eyelid ectropion repair using a lateral tarsal strip technique. METHODS: This is an Institutional Review Board-approved retrospective analysis of patients undergoing lower eyelid ectropion repair. This study included all patients from 2012 to 2018 operated on by a single surgeon at the University of Texas Southwestern Medical Center. For each patient, LCA, IOSE, and eyelid curvature were measured on preoperative and postoperative photographs using NIH Image J photographic analysis. These measurements were compared using paired 1-tail t-tests for LCA and IOSE and paired 2-tail t-tests for eyelid curvature. This study was Health Insurance Portability and Accountability Act-compliant with protection of individually identifiable information. RESULTS: Fifty-one patients with lower eyelid ectropion underwent lower eyelid ectropion repair using a lateral tarsal strip technique. Forty-three of the patients underwent a bilateral lower eyelid ectropion repair. There was no statistically significant difference in the LCA. There was a reduction in IOSE among both cohorts. The fourth degree polynomial trendlines generated to assess eyelid curvature demonstrated statistical significance, suggesting a flattening of eyelid curvature. margin-to-reflex distance 2 also had a statistically significant decrease postoperatively. CONCLUSIONS: Lower eyelid ectropion repair using a lateral tarsal strip approach causes a reduction in IOSE, a more gradual lower eyelid curvature, and a decrease in margin-to-reflex distance 2 without causing a statistically significant change in LCA.

[Toward a preventive management Alzheimer's disease]. / Pour une prise en charge préventive de la maladie d'Alzheimer.

Dementias, and Alzheimer's disease (AD) in particular, will increasingly become a public health issue. However, three major data may change the severity of these pathologies: in young adults, simple measures of healthy lifestyle (control of vascular risk factors, physical activity and cognitive stimulation), have an impact on a future cognitive decline; the same lifestyle interventions may delay the start of the disease for elderly people potentially at-risk; finally, and for the first time, a monoclonal antibody directed against amyloid lesions has just shown a significant effect on the progression of AD in patients at an early stage of the disease. According to these results, we will have to reconsider the strategy for managing minor or severe cognitive disorders and particularly AD. Nowadays, patients start the care process too late. The solution is to act earlier, even preventively. It is necessary to improve a care offer adapted to this new situation in order to impact on the disease as soon as possible, even before the onset of symptoms, based on: 1) predictive algorithms aimed at establishing whose cognitively unimpaired individuals may further develop the disease; these algorithms will be based on demographic, family, cognitive, genomic and biological data, such as in the "Santé Cerveau" project developed in partnership with the Health Regional Agency (ARS) and the general practitioners; 2)and on some expert centers which must become "dementia prevention clinics" to test prevention measures, initiate and validate multi-domain therapeutic education programs; to disclose about the risk in response to the request of worried patients; and to propose early pharmacological treatments if these individuals are on the way to declare AD in the coming months, taking into account competition between risks. This will allow to prepare to make use of new pharmacological treatments that might be discovered.

The impact of different classes of lupus nephritis on maternal and fetal outcomes: a cohort study of 147 pregnancies.

OBJECTIVE: To analyze the impact of different classes of lupus nephritis as risk variables for maternal and fetal adverse outcomes in a cohort of pregnant lupus patients. METHODS: This is a cohort study with retrospective and prospective data collection, conducted at the University Hospital of State University of Rio de Janeiro, Brazil, from 2011 to 2016. A total of 147 pregnancies of 137 systemic lupus erythematosus patients of whom 66 had lupus nephritis were included. Demographic and clinical features, as well as maternal and fetal outcomes were observed for each nephritis histological class among systemic lupus erythematosus patients and compared with those without nephritis. Categorical variables were expressed as absolute and relative frequencies and numerical variables as means and standard deviation. The chi-square test with Fisher's correction and Student's t-test were used for statistical analysis. A pvalue < 0.05 was considered statistically significant. RESULTS: Systemic lupus erythematosus patients with proliferative nephritis (classes III/IV, n = 54) presented more frequent disease flares ( p = 0.02), continuous active disease during pregnancy and puerperium ( p = 0.006), hospitalization due to systemic lupus erythematosus ( p < 0.001), hospitalization not directly associated to systemic lupus erythematosus ( p = 0.04), higher frequency of cesarean delivery ( p = 0.03) and preeclampsia ( p = 0.01) than patients without nephritis. Permanent damage measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was more frequent in classes III/IV than among the other patients. The frequency of adverse fetal outcomes such as prematurity and admission to neonatal intensive care unit were not different among systemic lupus erythematosus patients with or without nephritis. However, perinatal deaths were more frequent in patients with all classes of nephritis ( p = 0.003). CONCLUSION: Systemic lupus erythematosus patients with proliferative nephritis (classes III/IV) have a higher frequency of adverse maternal outcomes. This is probably due to the major impact of proliferative forms of nephritis on women's global heath, which is corroborated by the higher Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index findings, although we cannot exclude the negative influence of disease activity for the maternal adverse events. The findings indicate a need for further lupus nephritis classification beyond the nonspecific term nephritis in the context of lupus pregnancy as the impact on maternal and fetal outcomes varies according to histological class.

Factors associated with first thrombosis in patients presenting with obstetric antiphospholipid syndrome (APS) in the APS Alliance for Clinical Trials and International Networking Clinical Database and Repository: a retrospective study.

OBJECTIVE: To evaluate the subsequent rate of thrombosis among women with obstetric antiphospholipid syndrome (Ob-APS) in a multicentre database of antiphospholipid antibody (aPL)-positive patients, and the clinical utility of the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients. DESIGN: Retrospective study. SETTING: The Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository. POPULATION: Women with Ob-APS. METHODS: Comparison of clinical and laboratory characteristics and measurement of aGAPSS in women with Ob-APS, with or without thrombosis, after initial pregnancy morbidity (PM). MAIN OUTCOME MEASURES: Risk factors for thrombosis and aGAPSS. RESULTS: Of 550 patients, 126 had Ob-APS; 74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age at diagnosis of Ob-APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had a higher aGAPSS compared with women with Ob-APS alone [median 11.5 (4-16) versus 9 (4-13); P = 0.0089]. CONCLUSION: Based on a retrospective analysis of our multicentre aPL database, 63% of women with Ob-APS developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high-risk aPL profile increased the risk. Women with subsequent thrombosis after Ob-APS had a higher aGAPSS at entry to the registry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL-positive women. TWEETABLE ABSTRACT: More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.

Correction to: Diffusion tensor imaging (DTI) and Tractography of the spinal cord in pediatric population with spinal lipomas: preliminary study.

The article which was recently published contained error. The figures and figure captions were interchanged during the publication process of the paper.

Diffusion tensor imaging (DTI) and Tractography of the spinal cord in pediatric population with spinal lipomas: preliminary study.

PURPOSE: Diffusion tensor imaging (DTI) allows studying the micro and macro architecture. One of the major challenges in dysraphism is to know the morphologic organization of the spinal cord. In a preliminary work, spinal lipoma was chosen for analyzing the micro-architecture parameters and fiber morphology of the spinal cord by DTI with tractography. METHODS: Twelve patients (0-8 years) related to spinal lipomas treated between May 2017 and March 2018 were included. Tractography reconstruction of the conus medullaris of 12 patients were obtained using the MedINRIA software. The diffusion parameters have been calculated by Osirix DTImap plugin. RESULTS: We found a significant difference in the FA (p = 0.024) between two age groups (< 24 months old and > 24 months old). However, no significant differences in the mean values of FA, RD, and MD between the level of the lipoma and the level above were noted. The tractography obtained in each case was coherent with morphologic sequences and reproducible. The conus medullaris was deformed and shifted. Destruction or disorganization of fibers and any passing inside the lipomas was not observed. CONCLUSIONS: Tractography of the conus medullaris in a very young pediatric population (0-8 years old) with a spinal lipoma is possible, reproductive, and allows visualization of the spinal cord within the dysraphism. Analysis of the FA shows that the presence of a lipoma seems to have an effect on the myelination of the conus medullaris. It is during the probable myelination phase that the majority of symptoms appear. Is the myelination per se the cause?

Congenital syphilis: A prospective study of 22 cases diagnosed by PCR.

Congenital syphilis (CS) is caused by Treponema pallidum infection in utero. There is a need to develop new tools to diagnose CS: the diagnostic value of PCR is difficult to assess. The aim of this study was to describe the clinical and laboratory characteristics of mothers and infants with CS as diagnosed by PCR tests on various maternal and neonatal samples. PATIENTS AND METHODS: We included all infants epidemiologically linked to a mother diagnosed with syphilis whose samples were referred to the Syphilis Reference Center, and for whom at least one positive PCR result was obtained. RESULTS: Twenty-two mother-infant pairs (8.3%) with assay performed on samples from one to four different anatomic sites were included between February 2011 and April 2018. Seven mothers (31.8%) were born abroad, fifteen (68.2%) presented psychological and/or social problems, eight (36.4%) had not been screened for syphilis prior to delivery, and eleven (50%) were referred from French overseas departments or territories, or from the Paris region. Six infants (27.3%) were stillborn and six were born preterm, while fifteen infants (68.2%) presented clinical features of CS. All infants born preterm were symptomatic. Infant VDRL/RPR titer was no greater than four times that in the mother's serum, except in two cases. DISCUSSION: Lack of antenatal care, social disadvantage and psychological issues were common. There is a need for enhanced surveillance both in the French overseas departments/territories and in the Paris region. A larger study is required to assess the sensitivity and specificity of PCR. The best site for sampling has yet to be established. We recommend the collection of as many samples as possible to avoid underdiagnosis of CS.

Associations of ultra-processed food and drink products with asthma and wheezing among Brazilian adolescents.

BACKGROUND: Although both consumptions of ultra-processed products and asthma are common during adolescence, the epidemiological evidence in regarding their association is unclear. We investigated the associations of ultra-processed products consumption with asthma and wheezing in a representative sample of Brazilian adolescents. METHODS: We used data from a representative sample of 109 104 Brazilian adolescents enrolled in the National Survey of School Health, 2012. The consumption of ultra-processed products was based on the weekly consumption (0-2, 3-4, ≥5 d/wk) of sweet biscuits, salty biscuits, ultra-processed meats, sweets/candies, soft drinks, and packaged snacks over the previous 7 days. We also calculated an ultra-processed consumption score by adding partial scores corresponding to weekly frequency intake of each ultra-processed product. The ultra-processed consumption score ranged from 0 to 42, the higher score, the higher the intake of these products. The presence of wheezing in the previous 12 months and asthma at any time in the past was self-reported. RESULTS: The adjusted odds ratios of asthma comparing the extreme categories ranged from 1.08 (95% CI 1.03-1.13) for sweets/candies to 1.30 (1.21-1.40) for ultra-processed meats. Similar magnitude of associations was found for wheezing outcome. The ultra-processed consumption score was positively associated with the presence of asthma and wheezing in a dose-response manner. The adjusted OR of asthma and wheezing comparing highest to lowest quintile of ultra-processed consumption score was 1.27 (95% CI 1.15-1.41) and 1.42 (1.35-1.50), respectively. CONCLUSIONS: The consumption of ultra-processed products was positively associated with the presence of asthma and wheezing in adolescents.

Behavioral disorders: The 'blind spot' of neurology and psychiatry.

Behavioral disorders occupy the crossroads between neurology and psychiatry, and emerging disorders, such as frontotemporal lobar degeneration of genetic origin and autoimmune encephalitis, can present with both neurological and psychiatric signs. Thus, the primary aim of this introductory article is to review frequently encountered behavioral clinical features, such as apathy and agitation, and their related syndromes, including frontal and anterior temporal syndromes. These behavioral states and their underlying etiologies are also here illustrated with clinical case reports. In addition, this review highlights the idea that in order to progress in the understanding and management of behavioral disorders, there needs to be a strong interest towards developing new forms of cooperation between neurologists, psychiatrists and neuroscientists, such as those who work at university-based hospital neuropsychiatric clinical units.

Stent-based delivery of adeno-associated viral vectors with sustained vascular transduction and iNOS-mediated inhibition of in-stent restenosis.

In-stent restenosis remains an important clinical problem in the era of drug eluting stents. Development of clinical gene therapy protocols for the prevention and treatment of in-stent restenosis is hampered by the lack of adequate local delivery systems. Herein we describe a novel stent-based gene delivery platform capable of providing local arterial gene transfer with adeno-associated viral (AAV) vectors. This system exploits the natural affinity of protein G (PrG) to bind to the Fc region of mammalian IgG, making PrG a universal adaptor for surface immobilization of vector-capturing antibodies (Ab). Our results: 1) demonstrate the feasibility of reversible immobilization of AAV2 vectors using vector tethering by AAV2-specific Ab appended to the stent surface through covalently attached PrG, 2) show sustained release kinetics of PrG/Ab-immobilized AAV2 vector particles into simulated physiological medium in vitro and site-specific transduction of cultured cells, 3) provide evidence of long-term (12 weeks) arterial expression of luciferase with PrG/Ab-tethered AAV2Luc, and 4) show anti-proliferative activity and anti-restenotic efficacy of stent-immobilized AAV2iNOS in the rat carotid artery model of stent angioplasty.