An analytical strategy for challenging members of the microplastic family: Particles from anti-corrosion coatings.

Potentially hazardous particles from paints and functional coatings are an overlooked fraction of microplastic (MP) pollution since their accurate identification and quantification in environmental samples remains difficult. We have applied the most relevant techniques from the field of microplastic analysis for their suitability to chemically characterize anti-corrosion coatings containing a variety of polymer binders (LDIR, Raman and FTIR spectroscopy, Py-GC/MS) and inorganic additives (ICP-MS/MS). We present the basis of a possible toolbox to study the release and fate of coating particles in the (marine) environment. Our results indicate that, due to material properties, spectroscopic methods alone appear to be unsuitable for quantification of coating/paint particles and underestimate their environmental abundance. ICP-MS/MS and an optimized Py-GC/MS approach in combination with multivariate statistics enables a straightforward comparison of the multi-elemental and organic additive fingerprints of paint particles. The approach can improve the identification of unknown particles in environmental samples by an assignment to different typically used coating types. In future, this approach may facilitate allocation of emission sources of different environmental paint/coating particles. Indeed, future work will be required to tackle various remaining analytical challenges, such as optimized particle extraction/separation of environmental coating particles.

Does the built environment influence location- and trip-based sedentary behaviors? Evidence from a GPS-based activity space approach of neighborhood effects on older adults.

OBJECTIVE: Evidence on the influence of built environments on sedentary behaviors remains unclear and is often contradictory. The main limitations encompass the use of self-reported proxies of sedentary time (ST), the scarce consideration of the plurality of sedentary behaviors, and environmental exposures limited to the residential neighborhood. We investigated the relationships between GPS-based activity space measures of environmental exposures and accelerometer-based ST measured in total, at the place of residence, at all locations, and during trips. METHODS: This study is part of the CURHA project, based on 471 older adults residing in Luxembourg, who wore a GPS receiver and a tri-axial accelerometer during 7 days. Daily ST was computed in total, at the residence, at all locations and during trips. Environmental exposures included exposure to green spaces, walking, biking, and motorized transportation infrastructures. Associations between environments and ST were examined using linear and negative binomial mixed models, adjusted for demographics, self-rated health, residential self-selection, weather conditions and wear time. RESULTS: Participants accumulated, on average, 8 h and 14 min of ST per day excluding sleep time. ST spent at locations accounted for 83 % of the total ST. ST spent at the residence accounted for 87 % of the location-based ST and 71 % of the total ST. Trip-based ST represents 13 % of total ST, and 4 % remained unclassified. Higher street connectivity was negatively associated with total ST, while the density of parking areas correlated positively with total and location-based ST. Stronger associations were observed for sedentary bouts (uninterrupted ST over 20 and 30 min). CONCLUSION: Improving street connectivity and controlling the construction of new parking, while avoiding the spatial segregation of populations with limited access to public transport, may contribute to limit ST. Such urban planning interventions may be especially efficient in limiting the harmful uninterrupted bouts of ST among older adults.

Single-agent anti-PD-1 or combined with ipilimumab in patients with mucosal melanoma: an international, retrospective, cohort study.

BACKGROUND: Mucosal melanoma (MM) is a rare melanoma subtype with distinct biology and poor prognosis. Data on the efficacy of immune checkpoint inhibitors (ICIs) are limited. We determined the efficacy of ICIs in MM, analyzed by primary site and ethnicity/race. PATIENTS AND METHODS: A retrospective cohort study from 25 cancer centers in Australia, Europe, USA and Asia was carried out. Patients with histologically confirmed MM were treated with anti-programmed cell death protein 1 (PD-1) ± ipilimumab. Primary endpoints were response rate (RR), progression-free survival (PFS), overall survival (OS) by primary site (naso-oral, urogenital, anorectal, other), ethnicity/race (Caucasian, Asian, Other) and treatment. Univariate and multivariate Cox proportional hazards model analyses were conducted. RESULTS: In total, 545 patients were included: 331 (63%) Caucasian, 176 (33%) Asian and 20 (4%) Other. Primary sites included 113 (21%) anorectal, 178 (32%) urogenital, 206 (38%) naso-oral and 45 (8%) other. Three hundred and forty-eight (64%) patients received anti-PD-1 and 197 (36%) anti-PD-1/ipilimumab. RR, PFS and OS did not differ by primary site, ethnicity/race or treatment. RR for naso-oral was numerically higher for anti-PD-1/ipilimumab [40%, 95% confidence interval (CI) 29% to 54%] compared with anti-PD-1 (29%, 95% CI 21% to 37%). Thirty-five percent of patients who initially responded progressed. The median duration of response (mDoR) was 26 months (95% CI 18 months-not reached). Factors associated with short PFS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3 (P < 0.01), lactate dehydrogenase (LDH) more than the upper limit of normal (ULN) (P = 0.01), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). Factors associated with short OS were ECOG PS ≥1 (P < 0.01), LDH >ULN (P = 0.03), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). CONCLUSIONS: MM has poor prognosis. Treatment efficacy of anti-PD-1 ± ipilimumab was similar and did not differ by ethnicity/race. Naso-oral primaries had numerically higher response to anti-PD-1/ipilimumab, without difference in survival. The addition of ipilimumab did not show greater benefit over anti-PD-1 for other primary sites. In responders, mDoR was short and acquired resistance was common. Other factors, including site and number of metastases, were associated with survival.

Dorsal rhizotomy in cerebral palsy: How root sectioning is influenced by intraoperative neuromonitoring?

INTRODUCTION AND OBJECTIVE: Dorsal rhizotomy is a controversial procedure for treating spasticity in children with cerebral palsy, particularly regarding the influence of intraoperative neuromonitoring (ION). The objective of this study was to evaluate the influence of ION in adjusting root sectioning compared the preoperative program established by the multidisciplinary team. MATERIAL AND METHODS: Twenty-four consecutive children with spastic diplegia or quadriplegia, operated on between 2017 and 2020 in the University Hospital of Nancy, France, were studied. All underwent the same procedure: Keyhole Intralaminar Dorsal rhizotomy (KIDr) with enlarged multilevel interlaminar openings to access all roots from L2 to S2. The Ventral Root (VR) was stimulated to map radicular myotomes, and the Dorsal Root (DR) to test excitability of the segmental circuitry. Muscle responses were observed independently by the physiotherapist and by EMG-recordings. The study compared final root sectioning per radicular level and per side after ION versus the preoperative program determined by the multidisciplinary team. RESULTS: ION resulted in significant differences in final percentage root sectioning (P<0.05), with a decrease for L2 and L3 and an increase for L5. ION modified the symmetry of sectioning, with 32% instead of 5% in preoperative program. Only 5 children showed change in GMFC score 6 months after surgery. CONCLUSION: The use of ION during dorsal rhizotomy led to important modifications of root sectioning during surgery, which justifies individual control of each root, level by level and side by side, to optimize the therapeutic effect.

Ophthalmological lesions in shaken baby syndrome: A retrospective analysis of 133 consecutive cases (1992-2018).

INTRODUCTION: Shaken Baby Syndrome (SBS) is a non-accidental head trauma in which shaking causes cranio-cerebral lesions. Shaking can lead to ophthalmologic lesions such as retinal hemorrhage (RH). The aim of the present study was to compare our long-term results in to the literature data. PATIENTS AND METHODS: This study was a single-center retrospective descriptive analysis of 133 consecutive SBS cases (1992-2018). Only seniors in ophthalmology were authorized to perform these examinations. We studied type of lesion (retinal, intra-vitreal, papilledema), location (uni- or bi-lateral), and correlation with gender and age. Infants with a traumatic context without suspicion of child abuse were excluded. RESULTS: Mean age at diagnosis was 131days (range, 14days-10months). Boys accounted for 72.2% of the population. The prevalence of ophthalmologic lesions was 70.3%. 94.4% were RH; intra-vitreous hemorrhage (6.7%) and papilledema (11.1%) were less frequent. Lesions were bilateral in 81.1% of cases. Retinal lesions were classified in terms of location. Macular involvement was diagnosed in 8.2% of cases. 18.8% of retinal lesions could not be classified because of lack of precision in the ophthalmology report. The prevalence of ophthalmic lesions was higher for children aged over 6months: 80%. CONCLUSION: This series highlighted a high rate of ophthalmic lesions in SBS, with a high rate of bilateral involvement. RH was the most frequent lesion. RH in a context of subdural hematoma is a strong argument in favor of SBS. The forensic implications are that rigorous ophthalmologic examination by a senior practitioner is mandatory.

Prenatal neurosurgical counseling for conditions affecting the fetal nervous system.

OBJECTIVE: The aim of this study was to share a single center's experience of prenatal neurosurgical counseling and explore pregnant women's experiences with counseling. MATERIAL AND METHODS: This retrospective study analyzed data for 81 women who received prenatal counseling in a single institution (same senior pediatric neurosurgeon) over a 6-year period. Additionally, a retrospective questionnaire study was conducted with 33 women who chose to continue their pregnancy, to assess the strengths and weaknesses of counseling and analyze the reasons for their decision. RESULTS: Spinal dysraphism was the most frequent condition leading to prenatal counseling, followed by conditions affecting the cerebrospinal fluid. 57.6% of the women did not follow the French national recommendations on folic acid supplementation in the periconceptional period, and 38.3% underwent termination of pregnancy (TOP). One-third of the 33 women who answered our questionnaire changed their mind about TOP after counseling, and 50% reported that the information provided influenced their decision. CONCLUSION: Prenatal neurosurgical counseling is nowadays an important part of a pediatric neurosurgeon's practice. It provides specific information to the woman to decide whether to continue the pregnancy. Urological concerns are frequent among the malformations encountered. Hence, we conclude that these women should be offered the possibility of seeing a urologist. Areas for improvement include greater awareness regarding folic acid supplementation and improved psychological care. The advantage for a woman of consulting a neurosurgeon consists in receiving information that is as accurate as possible about the level of disability of the future child and about surgery and follow-up.

Late effects of craniospinal irradiation for medulloblastomas in paediatric patients.

Along with surgery, radiation therapy (RT) remains an essential option to cure patients suffering from medulloblastoma. However, its long-term adverse effects, particularly due to craniospinal irradiation (CSI), which is necessary to eradicate microscopic spread, are a limiting factor. The most frequent sequelae involve neurocognitive and endocrine impairment, which occurs in nearly all patients. Recent progress achieved through genetic and molecular biology offers the possibility to better stratify patients according to risk factors such as age, post-resection tumour residue and metastasis. Thus, new therapeutic studies assess the possibility to reduce radiation dose and/or radiation field size for patients with the most favourable prognosis. New radiotherapy techniques are also used such as Intensity-Modulated Radiotherapy (IMRT), tomotherapy and proton therapy, which aim at reducing the dose delivered to normal tissue. Conventional photon-based therapy has a relatively high exit dose in contrast with proton therapy which causes less damage to surrounding healthy tissue. It is noteworthy that each technique requires a long follow-up in order to prove that late effects could be reduced without compromising survival rates. Dosimetric comparison theoretically suggests that proton therapy may be the superior method for CSI in terms of late effects, but further research is needed to firmly establish this. Whatever the technique used, the great complexity of CSI requires discipline and expertise along with an external quality control online before the first RT session.

Surgical approach to the posterior fossa in children, including anesthetic considerations and complications: The prone and the sitting position. Technical note.

INTRODUCTION: Medulloblastoma (MB) in children is, in most cases, a midline lesion located in the posterior fossa, with a high tendency to invade the fourth ventricle (and sometimes its floor). METHODS: In this technical note, we present both the sitting and the prone position for children with medulloblastoma. These positions will be described together by deliberately deciding not to oppose one against the other. The park bench position, seldom used in pediatric neurosurgery is not described here. The latter procedure can be useful, however, for MB located more laterally or within the cerebellopontine angle. RESULTS: The aim of this technical note is to provide the reader with a step by step procedure (from installation to closure), at least from the author's point of view. A special focus regarding anesthetic considerations is also provided. This anesthesia requires perfect coordination and communication between both the anesthetic and surgical teams. Complications of posterior fossa surgery are mentioned as well. Some of the advantages and disadvantages of each positions are mentioned. CONCLUSION: Only careful installation, respect of certain surgical principles (careful attention of the vermis and dentate nuclei for example), knowledge of anatomy, closure and perioperative monitoring, screening and immediate correction of potentially devastating complications will enable surgeons to obtain the best results from their surgery.

The relationship between spontaneous cerebrospinal fluid leak and idiopathic intracranial hypertension.

Surgical treatment of spontaneous cerebrospinal fluid (CSF) leak is now performed by ENT surgeons, endonasal endoscopy being preferred to craniotomy as less invasive. However, it is often the symptom of underlying idiopathic intracranial hypertension, which lies outside the traditional sphere of ENT competence. Surgery is a necessary step, but should not obscure the need to treat the underlying pathology. This treatment is complex, and requires multidisciplinary team-work between otorhinolaryngologist, ophthalmologist, neurologist, neurosurgeon, radiologist, dietician, endocrinologist and psychotherapist. The present update details this multidisciplinary management to which the ENT surgeons must be attentive before and after spontaneous CSF leak repair.

Cerebellar swelling after surgery for medulloblastoma with leptomeningeal dissemination in children. A case based-update.

OBJECT: Despite the improvement in the overall management of medulloblastomas in recent years, certain phenomena and in particular postoperative cerebellar swelling remain an enigma. This rare complication, little described in the literature, is nonetheless life threatening for the patients. CASE REPORTS: We report our experience about two children who developed severe cerebellar swelling with hydrocephalus and upward herniation soon after a gross total resection of a fourth ventricle medulloblastoma by a telo-velar approach. Despite rapid management of ventricular dilation and optimal medical intensive treatment of intracranial hypertension, both children died quickly after the surgery. Pathological examination analyses were in favour of anaplastic/large cell medulloblastoma. DISCUSSION: Diffuse cerebellar swelling with upward herniation may occur postoperatively in young children with anaplastic/large cell medulloblastoma with leptomeningeal spread. In the literature, only 4 cases have been so far described with delayed onset of symptoms. Two children survived with an aggressive management (decompressive surgery and early radio-chemotherapy). CONCLUSION: Cerebellar swelling is an unrecognised and sudden complication of posterior fossa surgery for metastatic anaplastic medulloblastoma with leptomeningeal dissemination in young children. An initial less invasive surgical approach could be considered in such cases, in order to prevent this complication with potentially tragic issue, and which cannot be managed with a CSF shunt alone.

Optic pathway tumor in children: Toward a new classification for neurosurgical use.

OBJECT: Optic pathway tumors (OPT) represent a challenge for pediatric neurosurgeons. Role of surgery is debated due to the high risk of iatrogenic damage, and in lasts decades it lost its importance in favor of chemotherapy. However, in some cases surgery is necessary to make biomolecular and histological diagnosis, to manage intracranial hypertension (IH) and to cooperate with medical therapies in controlling tumor relapse. With the aim to standardize selection of surgical OPT cases, we propose a simple, practical and reproducible classification. METHODS: We retrospectively analyzed data of 38 patients with OPT treated at our institution (1990-2018). After careful analysis of MRI images, we describe a new classification system. Group 1: lesion limited to one or both optic nerve(s). Group 2: chiasmatic lesions extending minimally to hypothalamus. Group 3: hypothalamo-chiasmatic exophitic lesions invading the third ventricle; they can be further divided on the base of concomitant hydrocephalus. Group 4: hypothalamo-chiasmatic lesions extending widely in lateral direction, toward the temporal or the frontal lobes. Patients' data and adopted treatment are reported and analyzed, also depending on this classification. RESULTS: Twenty children were operated on for treatment of OPT during the study period. Permanent clinical impairment was noted in 5 (25%) of operated patients, while visual improvement was noted in 1 patient. OS rate was 100% at 5 years, with a median follow up of 9 years (ranging from 2 to 23). Prevalence of intracranial hypertension and proportion of first-line surgical treatment decision were significantly higher in groups 3-4 compared to groups 1-2 (P<0.001 for both tests). CONCLUSION: Surgery can offer a valuable therapeutic complement for OPT without major risk of iatrogenic damage. Surgery is indispensable in cases presenting with IH, as in groups 3 and 4 lesions. Eligibility of patients to surgery can be based on this new classification system.

Diffuse infiltrative pontine glioma biopsy in children with neuronavigation, frameless procedure: A single center experience of 10 cases.

INTRODUCTION: This study presented pediatric DIPG 's biopsy with frameless Neuronavigation. PATIENTS AND METHODS: We report our experience about 10 patients who had Diffuse Intrinsic Pontine Glioma between 2014 and 2018. All patients were biopsied with BrainLab Varioguide Neuronavigation®. We always used fusion between specific CT Scan and MRI to selected target, made planning and biopsies. All patients were included in BIOMEDE after scientific and ethic discussions. We always selected a trans-cerebellar trajectory and made same procedure (lot of biopsies at one level). All patients have MRI at J1 to verify site of biopsy and to eliminate complication. RESULTS: The average age was 8.1 years. Symptoms were common with principally headaches and nystagmus. All biopsies were contributive for histopathological diagnosis and establish molecular profile for molecular study. We have no definitive morbidity and procedure duration was 93minutes in average. All MRI didn't showed intracranial complication after procedure and showed great precision of biopsy compared with the selected target. DISCUSSION: We reviewed the literature and compare our results with series of DIPG biopsies using stereotactic frame or robotic assisted frameless. It was a safe, accuracy and easiness procedure. We always have histopathological and molecular result to proceed next step of treatment. This modality is an alternative possibility to biopsy very young patients with low morbidity.

YAP/TAZ Regulate Elevation and Bone Formation of the Mouse Secondary Palate.

Clefting of the secondary palate is one of the most common congenital anomalies, and the multiple corrective surgeries that individuals with isolated cleft palate undergo are associated with major costs and morbidities. Secondary palate development is a complex, multistep process that includes the elevation of the palatal shelves from a vertical to horizontal position, a process that is not well understood. The Hippo signaling cascade is a mechanosensory pathway that regulates morphogenesis, homeostasis, and regeneration by controlling cell proliferation, apoptosis, and differentiation, primarily via negative regulation of the downstream effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). We deleted Yap/Taz throughout the palatal shelf mesenchyme as well as specifically in the posterior palatal shelf mesenchyme, using the Osr2Cre and Col2Cre drivers, respectively, which resulted in palatal shelf elevation delay and clefting of the secondary palate. In addition, the deletion resulted in undersized bones of the secondary palate. We next determined downstream targets of YAP/TAZ in the posterior palatal shelves, which included Ibsp and Phex, genes involved in mineralization, and Loxl4, which encodes a lysyl oxidase that catalyzes collagen crosslinking. Ibsp, Phex, and Loxl4 were expressed at decreased levels in the ossification region in the posterior palatal shelf mesenchyme upon deletion of Yap/Taz. Furthermore, collagen levels were decreased specifically in the same region prior to elevation. Thus, our data suggest that YAP/TAZ may regulate collagen crosslinking in the palatal shelf mesenchyme, thus controlling palatal shelf elevation, as well as mineralization of the bones of the secondary palate.

Sox2 Controls Periderm and Rugae Development to Inhibit Oral Adhesions.

In humans, ankyloglossia and cleft palate are common congenital craniofacial anomalies, and these are regulated by a complex gene regulatory network. Understanding the genetic underpinnings of ankyloglossia and cleft palate will be an important step toward rational treatment of these complex anomalies. We inactivated the Sry (sex-determining region Y)-box 2 (Sox2) gene in the developing oral epithelium, including the periderm, a transient structure that prevents abnormal oral adhesions during development. This resulted in ankyloglossia and cleft palate with 100% penetrance in embryos examined after embryonic day 14.5. In Sox2 conditional knockout embryos, the oral epithelium failed to differentiate, as demonstrated by the lack of keratin 6, a marker of the periderm. Further examination revealed that the adhesion of the tongue and mandible expressed the epithelial markers E-Cad and P63. The expanded epithelia are Sox9-, Pitx2-, and Tbx1-positive cells, which are markers of the dental epithelium; thus, the dental epithelium contributes to the development of oral adhesions. Furthermore, we found that Sox2 is required for palatal shelf extension, as well as for the formation of palatal rugae, which are signaling centers that regulate palatogenesis. In conclusion, the deletion of Sox2 in oral epithelium disrupts palatal shelf extension, palatal rugae formation, tooth development, and periderm formation. The periderm is required to inhibit oral adhesions and ankyloglossia, which is regulated by Sox2. In addition, oral adhesions occur through an expanded dental epithelial layer that inhibits epithelial invagination and incisor development. This process may contribute to dental anomalies due to ankyloglossia.

Influence of Natural Polyphenols on Isolated Yeast Dipodascus magnusii Mitochondria.

The effect of stilbene polyphenols (resveratrol and pinosilvin) and flavonoids (dihydromyricetin, epigallocatechin, and dihydroquercetin) on producing the reactive oxygen species (ROS) due to cell respiration using the isolated mitochondria of the fungus Dipodascus (Endomyces) magnusii was studied. It was shown that the inhibition of the ROS generation with stilbenes is related to both the oxygen consumption inhibition and their antioxidant properties. The degree of manifestation of polyphenol antioxidant properties depended on the number of hydroxyl groups in a polyphenol molecule. Of the flavonoids tested, dihydromyricetin was most active in reducing the ROS generation, but its inhibitory effect on oxygen consumption by mitochondria was significantly lower as compared to that of the stilbenes. The data obtained show that the mechanism of reducing the ROS generation with polyphenols is associated with both the respiratory inhibition and their antioxidant properties.

Label reading, numeracy and food & nutrition involvement.

The purpose of this study was to investigate objective performance on a nutrition label comprehension task, and the influence of numeracy and food-related involvement on this performance level. A pilot study (n = 45) was run to prepare the scales in French. For the main study (n = 101), participants provided demographic information and answered the nutrition label survey, the short numeracy scale and two different food-related involvement scales (i.e. the food involvement scale and the nutrition involvement scale). Both studies were conducted online, and consent was obtained from all participants. Participants answered correctly only two-thirds of the nutrition label task items. Numeracy and food involvement scores were positively correlated with performance on this task. Finally, food involvement interacted with numeracy. Specifically, people scoring low in numeracy performed generally more poorly on the task, but if they had high food involvement scores, their performance increased. This suggests that high food-related motivation may compensate for poor numeracy skills when dealing with nutrition labels.