Early nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs

IFN-I and IFN-III immunity in the nasal mucosa is poorly characterized during SARS-CoV-2 infection. We analyze the nasal IFN-I/III signature, namely the expression of ISGF-3–dependent IFN-stimulated genes, in mildly symptomatic COVID-19 patients and show its correlation with serum IFN-α₂ levels, which peak at symptom onset and return to baseline from day 10 onward. Moreover, the nasal IFN-I/III signature correlates with the nasopharyngeal viral load and is associated with the presence of infectious viruses. By contrast, we observe low nasal IFN-I/III scores despite high nasal viral loads in a subset of critically ill COVID-19 patients, which correlates with the presence of autoantibodies (auto-Abs) against IFN-I in both blood and nasopharyngeal mucosa. In addition, functional assays in a reconstituted human airway epithelium model of SARS-CoV-2 infection confirm the role of such auto-Abs in abrogating the antiviral effects of IFN-I, but not those of IFN-III. Thus, IFN-I auto-Abs may compromise not only systemic but also local antiviral IFN-I immunity at the early stages of SARS-CoV-2 infection.     

Healthy school meals and educational outcomes

This paper provides field evidence on the effects of diet on educational outcomes, exploiting a campaign lead in the UK in 2004, which introduced drastic changes in the meals offered in the schools of one borough - Greenwich - shifting from low-budget processed meals towards healthier options. We evaluate the effect of the campaign on educational outcomes in primary schools using a difference in differences approach; comparing educational outcomes in primary schools (Key Stage 2 outcomes more specifically) before and after the reform, using the neighbouring Local Education Authorities as a control group. We find evidence that educational outcomes did improve significantly in English and Science. We also find that authorised absences - which are most likely linked to illness and health - fell by 14%.     

Cancer net survival on registry data: Use of the new unbiased Pohar‐Perme estimator and magnitude of the bias with the classical methods

Net survival, the survival which might occur if cancer was the only cause of death, is a major epidemiological indicator required for international or temporal comparisons. Recent findings have shown that all classical methods used for routine estimation of net survival from cancer‐registry data, sometimes called “relative‐survival methods,” provide biased estimates. Meanwhile, an unbiased estimator, the Pohar‐Perme estimator (PPE), was recently proposed. Using real data, we investigated the magnitude of the errors made by four “relative‐survival” methods (Ederer I, Hakulinen, Ederer II and a univariable regression model) vs. PPE as reference and examined the influence of time of follow‐up, cancer prognosis, and age on the errors made. The data concerned seven cancer sites (2,51,316 cases) collected by FRANCIM cancer registries. Net survivals were estimated at 5, 10 and 15 years postdiagnosis. At 5 years, the errors were generally small. At 10 years, in good‐prognosis cancers, the errors made in nonstandardized estimates with all classical methods were generally great (+2.7 to +9% points in prostate cancer) and increased in age‐class estimations (vs. 5‐year ones). At 15 years, in bad‐ or average‐prognosis cancers, the errors were often substantial whatever the nature of the estimation. In good‐prognosis cancers, the errors in nonstandardized estimates of all classical methods were great and sometimes very important. With all classical methods, great errors occurred in age‐class estimates resulting in errors in age‐standardized estimates (+0.4 to +3.2% points in breast cancer). In estimating net survival, cancer registries should abandon all classical methods and adopt the new Pohar‐Perme estimator.     

Ambrosia maritima L.: study of molluscicidal properties of several generations originating in Egypt and cultivated in Senegal

The authors experiment molluscicidal properties of Ambrosia maritima L. from Egypt and cultivated in Senegal. Four generations are tested. Six plants, on eight tested, had same molluscicidal activity as the strain in Egypt.     

Determination of RNA expression for cholecystokinin/gastrin receptors (CCKA,CCKB and CCKC) in human tumors of the central and peripheral nervous system

Gastrin (G17) belongs to the cholecystokinin (CCK) peptide family widely distributed in the brain, and we were the first to show that it significantly modulates the growth and migration features of tumor astyrocytes. Conflictual data have been published as to whether CCKA, CCKB and CCKC receptors are, or are not, present in tumors of the central and peripheral nervous system (CPNS) in general, and in gliomas in particular. In the present study we employed polymerase chain reaction (PCR) on a series of 29 CNPS tumors, including 20 gliomas (17 astrocytic and 3 oligodendroglial tumors), 4 schwannomas and 5 meningiomas to investigate whether RNAs were present or absent in the case of these CCKA, CCKB and CCKC receptors. The presence of the three CCK receptor subtypes was also assayed on three experimental models, i.e. the U373 human glioma, the C6 rat glioma and the 9L rat gliosarcoma. The data show that 9/20 (45%) of the gliomas exhibited RNAs for the CCKB receptor as did the C6 rat glioma, 13/20 (65%) RNAs for the CCKC receptor as did the U373 human glioma and the 9L rat gliosarcoma. Of the 20 gliomas, 17 (85%) expressed RNAs for either the CCKB or the CCKC receptor (or both), a feature which was also observed in the experimental models. One schwannoma and one meningioma exhibited RNAs for the CCKB receptor, while 4/4 schwannomas and 4/5 meningiomas showed RNAs for the CCKC receptor. None of the gliomas, schwannomas or meningiomas exhibited RNAs for the CCKA receptor, which were found in the 9L rat gliosarcoma model only. These data emphasize that 85% of the gliomas under study and 86% (25/29) of the tumors of the central and peripheral nervous system exhibited CCKB and/or CCKC receptors. This therefore suggests an important role for gastrin in the biological development of these tumors.     

Long-term results of tendon transfers in radial and posterior interosseous nerve paralysis

Eighteen cases of tendon transfer for isolated radial or posterior interosseous nerve palsy have been carried out in our unit over a period of 21 years. Fifteen patients were reviewed with a mean follow-up of 9.5 years. Nine had sustained high and six low radial nerve injury. We achieved 11 excellent, two good, one fair and one bad result. The main problems were loss of power of gripping and the occurrence of radial deviation, particularly in patients with flexor carpi ulnaris transfer to the extensor digitorum communis. During this time, our technique has evolved, including changes of the tendons transferred. Our final preference is a modified Tsuge procedure, using the pronator teres to restore extension of the wrist, the flexor carpi radialis for extension of the fingers and the palmaris longus for extension of the thumb. Abduction of the thumb is restored by a tenodesis of the abductor pollicis longus to the brachioradialis. This review justifies the final policy, in particular the preservation of flexor carpi ulnaris to maintain wrist stability and flexion.     

Les maladies auto-inflammatoires associées aux mutations de NLRC4 : revue systématique de la littérature

The auto-inflammatory diseases linked to NLRC4 mutations are recently described entities. Transmission is autosomal dominant in 80 % of cases; cases of somatic mutation have already been reported. The disease may display two very different clinical phenotypes: the phenotype 1 (30 %), severe, is dominated by a multisystemic inflammation starting in the first year of life with symptoms of chronic inflammatory bowel disease (IBD), macrophagic actication syndrome (MAS), or even a presentation suggesting a cryopyrinopathy in its CINCA form; the mortality of this phenotype is high (25 %). The phenotype 2 (70 %), mild, usually starts after the age of 3 and is characterized by cold urticaria, arthralgia, ocular features and fever in 50 % of cases without visceral failure. Anti-interleukin-1 inhibitors are effective in most cases (83 %). Interleukin-18 (IL-18) levels are very high in both clinical forms. Interleukin-18 inhibitors and anti-interferon-gamma inhibitors were remarkably effective in two very severe phenotype 1 patients. Thus, NLRC4 mutations can induce various clinical manifestations with two distinct phenotypes. Although still rare, because very recently described, this group of diseases could be evoked by an internist in front of cold familial urticarial; probably more and more cases will be diagnosed thanks to the major progresses of genetic diagnostic tools such as next generation sequencing.