Fetal MRI : an essential step in interpreting complex ultrasound findings

Background: Fetal magnetic resonance imaging (MRI) allows for the interpretation of complex fetal anomalies detected on ultrasound (US). Locally it has been available since 2013 but has remained underused. Method: In this paper we report the US and MRI findings of all cases of fetal MRI that were taken to date locally and how MRI can contribute to the clarification of malformations, management, counseling, evaluation of prognosis and ruling out of other possible malformations. Results: The cases reported were: two cases of hydroureter; gastroschisis; ventriculomegaly; intracranial haemorrhage; splenic cyst; Arnold Chiari II malformation. In all seven cases MRI was able to add to or change the diagnosis. Conclusion: Fetal MRI acts as an adjunct to US in interpreting abnormal fetal development. It is a safe non-invasive method of imaging that allows the clinician to take more informed decisions and better parental counselling.peer-reviewe

No rivals to the king: the limits to political reform in Morocco's "Enlightened Authoritarianism"

In Morocco it is still the king who defines the boundaries of political discourse and action. The palace is increasingly placing obstacles in the path of its strongest adversary, the moderate Islamist Justice and Development Party (PJD). This was seen most recently in the difficult and protracted coalition negotiations following the October 2016 parliamentary elections. At the same time, pressure on civil society critics is steadily intensifying. The inherent promise of political reform in Morocco’s comparatively inclusive model is increasingly eroding and gradually substituted with the promise of economic modernisation, potentially undermining the very bases of the kingdoms domestic stability. It is thus also in Europe’s interests for Morocco to uphold the progress it has achieved through the political reforms of recent decades. (author's abstract

Assessing the see-and-treat approach for the management of high-grade squamous intraepithelial cervical lesions

Objectives: To assess local histological outcomes in patients with HSIL cytology results on cervical smears, in both the see-and-treat and three-step approach. Study Design: A retrospective analysis of patients with HSIL on cervical cytology was performed, obtaining an 83 patient cohort. The histological result following the primary investigation (colposcopic-directed biopsy or excisional procedure) was noted for each patient together with their demographic variables and HPV status. Results: Of 83 patients with HSIL cytology on cervical smear, 43 underwent LLETZ as a primary procedure, while 40 patients underwent a colposcopic-directed biopsy. There was no statistically significant difference in terms of dermographics and HPV status between the two groups. In those patients who had LLETZ as a primary procedure, 29 had CIN2+ on histology. On the other hand, following colposcopic-directed biopsies, 17 resulted in CIN2+ on histology. Conclusion: The conventional approach within our local setting potentially has inferior sensitivity in picking up CIN2+ lesions when compared to the see-and-treat approach. On the other hand, primary excisional procedures were associated with an overtreatment rate of at least 20.9%, subjecting patients to unnecessary risks. Local improvement of colposcopic skill will aid to reduce this overtreatment rate and missed lesions at biopsy.peer-reviewe

Keine Konkurrenz für den König: Grenzen politischer Reformen in Marokkos "aufgeklärtem Autoritarismus"

In Marokko definiert der König nach wie vor den politischen Spielraum. Dabei legt der "Palast", eine gängige Chiffre für den König und sein Patronagenetzwerk, seinem stärk­sten Gegenspieler, der moderat islamistischen Partei für Gerechtigkeit und Entwicklung (PJD), immer mehr Steine in den Weg. Dies hat zuletzt die langwierige Regierungsbildung nach den Parlamentswahlen vom Oktober 2016 gezeigt. Auch der Druck auf zivilgesellschaftliche Kritiker steigt stetig. Indem das Versprechen politischer Reformen Schritt für Schritt durch ein Modernisierungsversprechen ersetzt wird, droht der rela­tiv inklusive Charakter des "marokkanischen Modells" verlorenzugehen - damit ent­fiele zugleich ein wichtiger Faktor für den inneren Frieden des Landes. Dass Marokko den Fortschritt nicht zurückdreht, der mit den Reformen der letzten Jahrzehnte erzielt wurde, liegt daher auch im Interesse europäischer Außenpolitik. (Autorenreferat

Cervical cancer : the importance of screening and vaccination

Cervical cancer is the fourth most common cancer in women worldwide and it is the most common cancer in women aged 15 to 44 years. The national cervical screening programme was introduced in Malta in 2016, aiming to increase the detection rate of pre-malignant, low- and high-grade cervical disease. The Human Papillonna Virus (HPV) is the main cause of cervical cancer and with the HPV vaccine as part of the national immunization programme, we have a strong and useful weapon in the prevention of infection with this virus.peer-reviewe

Alcohol consumption and lung cancer risk: A pooled analysis from the International Lung Cancer Consortium and the SYNERGY study

Background: There is inadequate evidence to determine whether there is an effect of alcohol consumption on lung cancer risk. We conducted a pooled analysis of data from the International Lung Cancer Consortium and the SYNERGY study to investigate this possible association by type of beverage with adjustment for other potential confounders. Methods: Twenty one case-control studies and one cohort study with alcohol-intake data obtained from questionnaires were included in this pooled analysis (19,149 cases and 362,340 controls). Adjusted odds ratios (OR) or hazard ratios (HR) with corresponding 95% confidence intervals (CI) were estimated for each measure of alcohol consumption. Effect estimates were combined using random or fixed-effects models where appropriate. Associations were examined for overall lung cancer and by histological type. Results: We observed an inverse association between overall risk of lung cancer and consumption of alcoholic beverages compared to non-drinkers, but the association was not monotonic. The lowest risk was observed for persons who consumed 10-19.9 g/day ethanol (OR vs. non-drinkers = 0.78; 95% CI: 0.67, 0.91), where 1 drink is approximately 12-15 g. This J-shaped association was most prominent for squamous cell carcinoma (SCC). The association with all lung cancer varied little by type of alcoholic beverage, but there were notable differences for SCC. We observed an association with beer intake (OR for >= 20 g/day vs nondrinker = 1.42; 95% CI: 1.06, 1.90). Conclusions: Whether the non-monotonic associations we observed or the positive association between beer drinking and squamous cell carcinoma reflect real effects await future analyses and insights about possible biological mechanisms

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 lineages has led to the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The subvariants BA.2.75.2 and BQ.1.1 are expected to become predominant in many countries in November 2022. They carry an additional and often redundant set of mutations in the spike, likely responsible for increased transmissibility and immune evasion. Here, we established a viral amplification procedure to easily isolate Omicron strains. We examined their sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost any antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remained weakly active. BQ.1.1 was also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals were low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increased these titers, which remained about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increased more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitated their spread in immunized populations and raises concerns about the efficacy of most currently available mAbs.N

Integrating new approaches to atrial fibrillation management: the 6th AFNET/EHRA Consensus Conference.

There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management, including the use of novel technologies and structured, integrated care, have the potential to enhance clinical phenotyping or result in better treatment selection and stratified therapy. Here, we report the outcomes of the 6th Consensus Conference of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new approaches to screening and diagnosis, enhancing integration of AF care, developing clinical pathways for treating complex patients, improving stroke prevention strategies, and better patient selection for heart rate and rhythm control. Ultimately, these approaches can lead to better outcomes for patients with AF

Genotypic and Phenotypic Characterization of P23H Line 1 Rat Model

The authors are grateful to Manuel Simonutti, Julie Dégardin, Jennifer Da Silva, Samantha Beck and Caroline Carvalho for their valuable help in phenotyping (platform of Institut de la Vision) and to Isabelle Renault, Léa Biedermann and André Tiffoche for animal care (platform of Institut de la Vision). The authors thank Stéphane Fouquet for his support in developing a custom-made Image J macro to measure thickness of retinal layers.This work was supported by Fondation Valentin Hauy (IA, EO), Retina France (IA, EO), e-rare RHORCOD (IA), Fondation de l’Oeil—Fondation de France (IA), Foundation Voir et Entendre (CZ), Foundation Fighting Blindness (FFB) (CD-CL-0808-0466-CHNO) (IA), and the FFB center grant (CD-CL-0808-0466-CHNO), Ville de Paris and Region Ile de France, Labex Lifesenses (reference ANR-10-LABX-65) supported by French state funds managed by the ANR within the Investissements d’Avenir programme (ANR-11-IDEX-0004-0), the Regional Council of Ile de France (I09–1727/R) (EO), the National Institute of Health grants EY10609 (MIN), EY001919 (MML) and EY006842 (MML) and the Foundation Fighting Blindness (MIN and MML).Rod-cone dystrophy, also known as retinitis pigmentosa (RP), is the most common inherited degenerative photoreceptor disease, for which no therapy is currently available. The P23H rat is one of the most commonly used autosomal dominant RP models. It has been created by incorporation of a mutated mouse rhodopsin (Rho) transgene in the wild-type (WT) Sprague Dawley rat. Detailed genetic characterization of this transgenic animal has however never been fully reported. Here we filled this knowledge gap on P23H Line 1 rat (P23H-1) and provide additional phenotypic information applying non-invasive and state-of-the-art in vivo techniques that are relevant for preclinical therapeutic evaluations. Transgene sequence was analyzed by Sanger sequencing. Using quantitative PCR, transgene copy number was calculated and its expression measured in retinal tissue. Full field electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT) were performed at 1-, 2-, 3- and 6-months of age. Sanger sequencing revealed that P23H-1 rat carries the mutated mouse genomic Rho sequence from the promoter to the 3’ UTR. Transgene copy numbers were estimated at 9 and 18 copies in the hemizygous and homozygous rats respectively. In 1-month-old hemizygous P23H-1 rats, transgene expression represented 43% of all Rho expressed alleles. ERG showed a progressive rod-cone dysfunction peaking at 6 months-of-age. SD-OCT confirmed a progressive thinning of the photoreceptor cell layer leading to the disappearance of the outer retina by 6 months with additional morphological changes in the inner retinal cell layers in hemizygous P23H-1 rats. These results provide precise genotypic information of the P23H-1 rat with additional phenotypic characterization that will serve basis for therapeutic interventions, especially for those aiming at gene editing.Yeshttp://www.plosone.org/static/editorial#pee