Signaling pathway deregulation and molecular alterations across pediatric medulloblastomas.

Medulloblastomas (MBs) account for 15% of brain tumors in children under the age of 15. To date, the overall 5-year survival rate for all children is only around 60%. Recent advances in cancer genomics have led to a fundamental change in medulloblastoma classification and is evolving along with the genomic discoveries, allowing to regularly reclassify this disease. The previous molecular classification defined 4 groups (WNT-activated MB, SHH-activated MB and the groups 3 and 4 characterized partially by NMYC and MYC driven MBs). This stratification moved forward recently to better define these groups and their correlation to outcome. This new stratification into 7 novel subgroups was helpful to lay foundations and complementary data on the understanding regarding molecular pathways and gene mutations underlying medulloblastoma biology. This review was aimed at answering the recent key questions on MB genomics and go further in the relevance of those genes in MB development as well as in their targeted therapies.

Impact of malpractice liability among spine surgeons: A national survey of French private neurosurgeons.

PURPOSE: In the general context of medical judicialization, spine surgeons are impacted by the part that medical responsibility and the risk of malpractice play in their actions and decisions. Our aim was to evaluate possible shifts in practices among private neurosurgeons who are highly exposed to this judicial risk and detect alterations in their pleasure in exercising their profession. We present the first national survey on French physicians' perception of surgical judicialization and consequences on their practice. METHODS: An online survey was submitted to the 121 members of the French Society of Private Neurosurgery, who represent 29.1% of the total number of spine surgeons and perform 36.0% of the national total spine surgery activity. The French law (no-fault out-of-court scheme) significantly impacts these surgeons in the event of litigation. RESULTS: A total of 78 surveys were completed (64.5% response rate): 89.7% of respondents experienced alteration of doctor-patient relationship related to judicialization and 60.2% had already refused to perform risky surgeries. Fear of being sued added negative pressure during surgery for 55.1% of respondents and 37.2% of them had already considered stopping their practice because of this litigation context. CONCLUSION: The increasing impact of medical liability is prompting practitioners to change their practice and perceptions. The doctor-patient relationship appears to be altered, negative pressure is placed on physicians and defensively, some neurosurgeons may refuse high-risk patients and procedures. This situation causes professional disenchantment and can ultimately prove disadvantageous for both doctors and patients.

Baseline status of policy and legislation actions to address non communicable diseases crisis in the Pacific.

BACKGROUND: Non-Communicable Diseases (NCD) are the leading cause of death in the Pacific Island Countries and Territories (PICTs) accounting for approximately 70% of mortalities. Pacific leaders committed to take action on the Pacific NCD Roadmap, which specifies NCD policy and legislation. To monitor progress against the NCD Roadmap, the Pacific Monitoring Alliance for NCD Action (MANA) was formed and the MANA dashboard was developed. This paper reports on the first status assessment for all 21 PICTs. METHODS: The MANA Dashboard comprises 31 indicators across the domains of leadership and governance, preventive policies, health system response and monitoring processes, and uses a 'traffic light' rating scheme to track progress. The dashboard indicators draw on WHO's best-buy interventions and track highly cost-effective interventions for addressing NCDs. The MANA coordination team in collaboration with national NCD focal points completed Dashboards for all 21 PICTs between 2017 and 2018 in an agreed process. The data were analysed and presented within each area of the MANA dashboard. RESULTS: This assessment found that PICTs are at varying stages of developing and implementing NCD policy and legislation. Some policy and legislation are in place in most PICTs e.g. smoke free environment (18 PICTs), alcohol licensing (19 PICTs), physical education in schools (14 PICTs), reduction of population salt consumption (14 PICTs) etc. However, no PICTs has policy or legislation on tobacco industry interference, controlling marketing of foods and drinks to children, and reducing trans-fats in the food supply, and only 7 PICTs have policies restricting alcohol advertising. Eighteen PICTs implement tobacco taxation measures, however only five were defined as having strong measures in place. Nineteen PICTs have alcohol taxation mechanisms and 13 PICTs have fiscal policies on foods to promote healthier diets. CONCLUSION: This baseline assessment fills a knowledge gap on current strengths and areas where more action is needed to scale up NCD action in a sustained 'whole of government and whole of society approach' in PICTs. The findings of this assessment can be used to identify priority actions, and as a mutual accountability mechanism to track progress on implementation of NCD policy and legislation at both national and Pacific level.

High Prevalence of Non-Communicable Disease Risk Factors among Adolescents in Pohnpei, Micronesia.

Non-communicable disease (NCD) related behaviors among adolescents are on the rise globally and in the Pacific region. To better understand and elucidate the prevalence of NCD risk factors among adolescents in Pohnpei state, Federated States of Micronesia, a cross-sectional study was conducted among secondary school students. Of 2965 students enrolled in the 2015-2016 academic year, 2555 (86.2%) completed the survey, and 2386 (80.5%) were included in the final analysis. Of the survey respondents, 21.7% of students self-reported smoking tobacco in the past 30 days, 30.3% self-reported drinking alcohol in the past 30 days, 40.9% self-reported chewing betel nut in the past 30 days, and 21.2% self-reported chewing tobacco with or without betel nut in the last 30 days. Male students, older students, and public school students had higher prevalence of substance use. Additionally, about 17.3% of students were overweight and 10.1% were obese according to physical measures of height and weight. Female students and private school students had higher prevalence of overweight and obesity than male students, and prevalence of overweight was higher in older age groups. These findings indicate a cohort of adolescents at substantial risk for the development of NCDs and signal an urgent need for public health interventions to address NCD risk factors.

[Treatment of intra-articular malunion of the distal radius of young active patients]. / Traitement des cals vicieux articulaires de l'extrémité distale du radius du sujet jeune actif.

Management of malunion of the distal radius remains difficult. Planning of the correction of the articular displacement requires a comprehensive analysis by CT arthrography to analyze bone, cartilage and ligaments. Arthroscopy is a valuable tool in the context of joint trauma. In the absence of osteoarthritis, the correction can be carried out as early as possible in the weeks or months following the initial fracture. The use of locking plates allows early mobilization after surgery. This correction aims to prevent the development of secondary osteoarthritis.

[Treatment of partial articular fractures of the distal radius in active young adults]. / Traitement des fractures articulaires partielles de l'extrémité distale du radius du sujet jeune actif.

The wrist's function is at stake in young active adults with partial intra-articular fractures of the distal radius. The high energy nature of these injuries, displaced fractures with risk of malunion in case of insufficient treatment, and associated ligament or cartilage damage all hinder the prognosis of these fractures. Many classification systems exist to help us analyze and in some cases, select a treatment. Optimal management requires a high-quality preoperative assessment and a precise surgical technique coupled with the use of arthroscopy to deal with joint and ligament injuries in the same operation. Devices that address the fragmented nature of these fractures provide the best fixation. The primary treatment goal is reduction with less 1mm intra-articular step-off in order to reduce the risk of secondary osteoarthritis and to treat associated ligament damage, which is very common and often under-estimated. Treating the fracture and any associated lesions during the same operation is the best way to ensure a good functional outcome.

Intraoperative monitoring by imaging and electrophysiological techniques during giant intracranial aneurysm surgery.

Difficulties in giant intracranial aneurysm surgery are the consequence of aneurysmal wall histology and the complex angioarchitecture of the vascular tree. In order to reduce complications and risks of those procedures, various imaging and electrophysiological techniques can be implemented perioperatively. The authors review the principles, goals and main results in this context of micro-Doppler and flowmeter techniques, near-infrared spectroscopy, operative microscope-integrated indocyanine green video-angiography, neuro-endoscopy, selective intraoperative angiography and electrophysiological monitoring.

Evaluation of the ventro 20° rostral-dorsocaudal oblique radiographic projection for the investigation of canine nasal disease.

OBJECTIVE: To assess the ventro 20° rostral-dorsocaudal oblique projection for canine nasal disease as an alternative to the dorsoventral intra-oral view. MATERIALS AND METHODS: Thirty-one dogs with nasal disease underwent radiography and computed tomography with a final diagnosis of underlying cause achieved through rhinoscopy, biopsy or cytology. Three independent observers, blinded to diagnosis, reviewed the nasal radiographs on two separate occasions. Intra- and inter-observer agreement and level of confidence on radiographic diagnosis were evaluated and radiographic diagnosis was compared with computed tomography and definitive diagnosis. RESULTS: The ventro 20° rostral-dorsocaudal oblique projection of canine nasal cavities was feasible in anaesthetised dogs and gave diagnostic quality images in most dogs. Assessment of this view showed moderate to substantial agreement with computed tomography diagnosis but gave lower confidence in diagnosis. Interpretation of this radiographic projection had substantial to almost perfect repeatability but moderate reproducibility. CLINICAL SIGNIFICANCE: The ventro 20° rostral-dorsocaudal oblique projection may be used as a valuable initial screening tool for canine nasal pathology in practices without access to advanced imaging, although computed tomography is still likely to provide greater diagnostic information.

Mapping HPV Vaccination and Cervical Cancer Screening Practice in the Pacific Region-Strengthening National and Regional Cervical Cancer Prevention.

OBJECTIVE: To provide background information for strengthening cervical cancer prevention in the Pacific by mapping current human papillomavirus (HPV) vaccination and cervical cancer screening practices, as well as intent and barriers to the introduction and maintenance of national HPV vaccination programmes in the region. MATERIALS AND METHODS: A cross-sectional questionnaire-based survey among ministry of health officials from 21 Pacific Island countries and territories (n=21). RESULTS: Cervical cancer prevention was rated as highly important, but implementation of prevention programs were insufficient, with only two of 21 countries and territories having achieved coverage of cervical cancer screening above 40%. Ten of 21 countries and territories had included HPV vaccination in their immunization schedule, but only two countries reported coverage of HPV vaccination above 60% among the targeted population. Key barriers to the introduction and continuation of HPV vaccination were reported to be: (i) Lack of sustainable financing for HPV vaccine programs; (ii) Lack of visible government endorsement; (iii) Critical public perception of the value and safety of the HPV vaccine; and (iv) Lack of clear guidelines and policies for HPV vaccination. CONCLUSION: Current practices to prevent cervical cancer in the Pacific Region do not match the high burden of disease from cervical cancer. A regional approach, including reducing vaccine prices by bulk purchase of vaccine, technical support for implementation of prevention programs, operational research and advocacy could strengthen political momentum for cervical cancer prevention and avoid risking the lives of many women in the Pacific.

Synchrotron radiation X-ray phase micro-computed tomography as a new method to detect iron oxide nanoparticles in the brain.

PURPOSE: The purpose of this study was to introduce synchrotron radiation X-ray phase computed tomography (SR-PCT) as a new method of visualizing ultrasmall superparamagnetic particles of iron oxide (USPIO) distribution into the brains of mice with neuroinflammation. PROCEDURES: The sensitivity of the technique was assessed by performing back-to-back SR-PCT and magnetic resonance imaging (MRI) in mice stereotaxically injected with a range of USPIO concentrations. Eight mice with cerebral ischemia were then intravenously injected with USPIOs and imaged back-to-back with MRI and SR-PCT. RESULTS: SR-PCT proved sensitive enough to detect iron in nanomolar quantities. In stroke-induced animals, SR-PCT showed hyperintense areas in the regions of MR signal loss and immunostaining for macrophages. SR-PCT, moreover, identified brain anatomy as clearly as histology, without the need for sectioning or staining, with an examination time of 44 min per brain at an isotropic spatial resolution of 8 µm. CONCLUSION: SR-PCT has potential for cellular imaging in intact brain, with unequaled neuroanatomy.

[Reconstruction of the cranial vault using CAD/CAM-fabricated glass bioceramic implants]. / Reconstruction de la voûte crânienne à l'aide de prothèses vitrocéramiques sur mesure.

BACKGROUND AND PURPOSE: Reconstruction of a cranial vault after craniectomy is an esthetic and functional challenge. The quest for the ideal implant that would mimic an original bone graft has tested many materials such as bone implants and artificial substitutes. The aim of this multicenter study was to report a set of preliminary results of cranioplasty using bioceramic implants made of Bioverit® II. METHODS: In this retrospective study, we attempted to assess the esthetic results of prefabricated Bioverit® II prostheses and to determine their performance in reducing operating time and surgical complications in delayed cranioplasty. RESULTS: Within a 3-year period, 16 patients from four French university hospitals underwent cranial reconstruction using this technique. The results were encouraging, with all patients showing a good esthetic outcome. Hospital length of stay after surgery was short (median, 5.5 days). One prosthesis had to be reshaped during surgery. Only one patient experienced superficial wound infection successfully treated without removing the material. CONCLUSIONS: CAD/CAM-fabricated Bioverit® II prostheses are a good alternative when autologous bone is not available. Fabrication of bioceramic prostheses using this method requires surgical scheduling, which is justified by the following advantages: reduced operating time, lack of donor morbidity, good esthetic results, and stability. The only drawback of this material is its price, which can limit its deployment.

Carcinoma de Células Escamosas de Tiroides: A Propósito de un Caso / Primary squamous cell thyroid carcinoma

El carcinoma de células escamosas de tiroides (CCET) es un tumor infrecuente y agresivo. Su etiología es incierta. Ante la presencia de carcinoma escamoso en la glándula tiroides debe excluirse la posibilidad de infiltración de un tumor originado en una estructura adyacente o de metástasis de otros carcinomas. El tratamiento de elección es la cirugía radical. La mayoría de los pacientes fallecen antes del año debido a progresión local de la enfermedad. Presentamos el caso de un paciente con una masa tiroidea, con diagnóstico histológico de carcinoma escamoso (con inmunohistoquímca negativa para tiroglobulina, TTF1 y calcitonina y positiva para p63 y citok5). Los estudios clínicos, endoscópicos y radiológicos excluyeron otros sitios de origen de carcinoma escamoso. Fue tratado con quimio y radioterapia, falleciendo por progresión local luego de 9 meses.

Primary squamous cell thyroid carcinoma (PSCTC) is a rare and aggressive tumor of uncertain origin. When squamous carcinoma is diagnosed, it is mandatory to exclude the possibility of primary tumor arising from an adjacent structure or representing metastases from a primary growth elsewhere. Aggressive surgical resection is the treatment of choice. However, the prognosis is poor, with a median survival of less than a year. Death is usually secondary to progression of local disease. We report a case of a patient presenting with a thyroid mass; biopsy was consistent with squamous cell carcinoma. On immunohistochemistry tumor cells were negative for TTF1, thyroglobulin and calcitonin. Cancer cells were positive for p63 and citok5. Extensive workup excluded the possibility of extrathyroid origin. The patient was treated with chemoradiotherapy; he died 9 months later due to local progression.

[Dosimetric stereotactic radiosurgical accident: Study of 33 patients treated for brain metastases]. / Traitement des métastases cérébrales par radiochirurgie stéréotaxique : étude de 33 cas liés à un accident de "surexposition".

The consequences of a dosimetric radiosurgery accident are not the same as a conventional radiotherapy accident. The objective of this study was to estimate the clinical and radiological outcome of patients treated by radiosurgery for metastasis during the period of the overexposure accident that occurred in the Toulouse Radiosurgery Unit. Between April 2006 and March 2007, 33 patients with 57 metastases were treated in the Toulouse Radiosurgery Unit (Novalis(®), BrainLab). An initial error in the estimation of the scatter factors led to an overexposure to radiation. The median age was 55 years [range, 35-85]. Twenty-one patients (64%) harbored a single metastasis. The primary tumor location was lung (16 cases), kidney (nine cases), breast (four cases), and others (four cases). The mean tumoral volume was 3.2cm(3) [0.04-14.07]. The mean prescribed dose at the isocenter was 20 Gy [range, 10-23], the mean delivered dose was 31.5 Gy [range, 13-52], and the mean overdose was 61.2% [range, 5.6-226.8]. In order to evaluate the consequences of the overdose, three parameters were analyzed: a risk index using dose and volume, the volume of parenchyma that received more than 12 Gy, and the mean dose in a sphere of 20cm(3) surrounding the target volume. Median actuarial survival was 14.1 months, the survival rate was 79.4 % at six months, 59.1% at 12 months, and 27.2% at 24 months. The rate of tumor control was 80.7%. No morbidity was observed. There was no correlation between death and the parameters studied. The survival rates and times observed in our study of the patients treated for brain metastases by radiosurgery and overexposed were among the good results of the international literature. Deaths were not related to the overdose and no side effect was noted. This dosimetric accident has not had worse consequences in this population.

Advanced QSRR modeling of peptides behavior in RPLC.

In QSRR the retention is modeled as a function of structural or molecular descriptors. Since the structural datasets can be very large a selection of informative variables is often required. But beside the question which subset of variables (descriptors) produces optimum predictions one should answer the question: can good prediction be used in the QSRR community even if the physical meaning of applied descriptors is hard to interpret? The main focus in this paper is put on different modeling methodologies applied and molecular descriptors used in the QSRR approaches. Besides the widely used multiple linear regression (MLR), these methodologies include partial least squares (PLS), uninformative variable elimination partial least squares (UVE-PLS), genetic algorithms (GA) prior to MLR or PLS. The comparison will focus on the predictive performance but also on the descriptors found to be most important for the chromatographic retention prediction of peptides. The results of this study showed that stepwise-MLR and UVE-PLS are producing better predictions than the rest of the studied methodologies. From the variables selected by various methodologies one can see that the important information for the retention mechanism of RPLC was given by 2D-, 3D-descriptors and descriptors from the empirical QSRR equations, which bring the information about hydrogen-bonding properties, molecular size, and complexity. Overall, for the considered data set the empirical QSRR models were predicting the peptides retention best.

Expression of c-Myc, neurofibromatosis Type 2, somatostatin receptor 2 and erb-B2 in human meningiomas: relation to grades or histotypes.

Meningiomas, which originate from arachnoid cells, represent one of the largest subgroups of intracranial tumors. They are generally benign, but can progress to malignancy. The aim of our study was to determine the expression of 4 genes, c-Myc, neurofibromatosis Type 2 (NF2), somatostatin receptor isoform 2 (sst2) and erb-B2, that have been associated with tumorogenesis or, possibly, with aggressive behavior or recurrence of meningiomas. We measured levels of mRNAs coding for these genes by qRT-PCR in 51 cases and levels ofc-Myc protooncogene and sst2 protein by immunohistochemistry in 26 cases of meningiomas of various grades and histotypes. C-Myc mRNA and protein levels were not grade-related, but validated subdivision of the 36 benign meningiomas into two groups, Groups IA and IB, based on histological and clinical features (Ki-67-proliferative index, absence or presence of mitoses, rate of recurrence and incidence of perilesional edema). In addition to histopathological grading, c-Myc expression may be useful in predicting tumor recurrence in patients with low-grade meningiomas. NF2 mRNA levels and sst2 mRNA and receptor levels were not grade-related, but were histotype-related, with significantly higher levels in the meningothelial subtype than in the fibroblastic subtype. Erb-B2 mRNA levels were not grade- or histotype-related. Furthermore, the high expression of sst2 in meningothelial meningioma suggests the possibility of a different tumorigenesis process in this meningioma subtype and may open perspectives for the diagnosis and therapy of this subtype using somatostatin as an antiproliferative agent.

[External radiotherapy and photodynamic therapy for esophageal carcinoma: a dangerous association?]. / Radiothérapie externe et photothérapie dynamique des cancers de l'oesophage: une association dangereuse ?

A 60-year-old man presented an oesophageal transmural necrosis fistulised in the trachea following curative photodynamic therapy (PDT) for a superficial recurrence of an oesophageal carcinoma, initially treated by radiochemotherapy. Two stents, a tracheal and an oesophageal one, were placed. Eight months later the patient is in complete remission with only mild swallowing problems. This complication, although unusual, has already been described by other teams with the association of radiochemotherapy and PDT. The present case study suggests that illumination dose should be lowered in this indication.

Ulithi Atoll health assessment: a peek at the health of rural Micronesia.

BACKGROUND: The health challenges of Micronesians are generally well known. However most of the health-related data collection occurs in the population centers and relatively little is known about the health of the residents of Micronesia's rural outer islands. This is of particular concern in the Federated States of Micronesia (FSM) where a large portion of the population lives on the outer islands. To gain a better understanding of the health issues facing the isolated outer islands of Micronesia, a health survey was performed on Ulithi Atoll in Yap, FSM. METHODS: A survey was created by the Yap State Department of Health Services and members of the Ulithian community. The survey was carried out on two of the four inhabited islands of Ulithi Atoll in July 2004. Both island communities actively participated in the survey providing translation and data gathering assistance. RESULTS: It was estimated that a >90% response rate for both islands was achieved. Analysis demonstrated that relative to the U.S., the Atoll's population experienced high rates of obesity (45%), hypertension (29%), and smoking (55%). Sixty-six percent of men surveyed reported alcohol use versus 16% of women. Use of alcohol was markedly lower on Fatharai Island where a Chief had mandated abstinence. Preventative health screening was limited with over 80% of women having pap smear in the past 2 years. In addition, the community identified finances and transportation as the main difficulties in accessing healthcare. CONCLUSION: Overall, the research identified a number of health issues that require closer attention, in particular hypertension, overweight, obesity, alcohol misuse, smoking prevalence, betel nut/ tobacco chewing, and domestic violence. There is indication that the community may be ready to address some of these issues. The value of community action within cultural frameworks is apparent, and there may be potential to extend culturally-based approaches to address a broader range of issues.