Increasing COVID-19 vaccination in the United States: projected impact on cases, hospitalizations, and deaths by age and racial group.

OBJECTIVES: Minority populations in the United States face a disproportionate burden of illness from COVID-19 infection and have lower vaccination rates compared with other groups. This study estimated the equity implications of increased COVID-19 vaccination in the United States, with a focus on the number of cases, hospitalizations, and deaths avoided. STUDY DESIGN: This was an observational real-world modeling study. METHODS: Data from the Centers for Disease Control and Prevention (CDC) were used to identify the remaining unvaccinated US population by county, age, and race as of October 22, 2021. The number of COVID-19 cases, hospitalizations, and deaths avoided were calculated based on case incidence and death data from the CDC, along with data on race- and age-specific hospitalization multipliers, under a scenario in which half of the remaining unvaccinated population per county, race, and age group obtained a full vaccine regimen. RESULTS: Vaccinating half of the remaining unvaccinated population in each age and race subgroup within counties would result in an estimated 22.09 million COVID-19 cases avoided, 1.38 million hospitalizations avoided, and 150,000 deaths avoided over 12 months. Some minority groups, particularly Black and Hispanic/Latino populations, were projected to experience substantial benefits from increased vaccination rates as they face both lower vaccination rates and worse outcomes if infected with COVID-19. CONCLUSIONS: Increasing COVID-19 vaccination in the United States not only benefits the population as a whole but also serves as a potentially useful lever to reduce the disproportionate burden of COVID-19 illness among minority populations.

Neutrophil-to-lymphocyte ratio (NLR) variations in relationship with childhood maltreatment in patients with anorexia nervosa: a retrospective cohort study.

PURPOSE: Anorexia nervosa (AN) is a serious mental illness. It is frequently accompanied by a history of childhood maltreatment (CM) that may constitute a specific ecophenotype in patients with eating disorders necessitating special assessment and management. This retrospective study tested whether in patients with AN, CM-related chronic stress may manifest through low-grade inflammation reflected by an increase in white blood cell ratios (neutrophil-to-lymphocyte ratio, NLR, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio). METHODS: Participants (N = 206) were enrolled at an eating disorder daycare unit in Montpellier, France, from March 2013 and January 2020. CM was assessed using the childhood trauma questionnaire (CTQ). The Eating Disorder Examination Questionnaire (EDE-Q) and the MINI were used to assess AN severity and the other clinical characteristics, respectively. RESULTS: NLR was higher in patients with AN and history of CM (p = 0.029) and in patients with AN and history of emotional abuse (p = 0.021), compared with patients with AN without history of CM. In multivariate analysis, emotional abuse (ß = 0.17; p = 0.027) contributed significantly to NLR variability. CONCLUSION: In patients with AN, NLR is a low-grade inflammation marker that is influenced by various sociodemographic, clinical and biological factors. It is more directly affected by some CM types, especially emotional abuse, than by the presence/absence of CM history. Future studies should focus on mediators between CM and increased inflammation, such as interoceptive awareness, emotional dysregulation, food addiction, and stress sensitization. LEVEL OF EVIDENCE: III. Evidence obtained from well-designed cohort or case-control analytic studies.

PI3K functions as a hub in mechanotransduction.

Mammalian cells integrate different types of stimuli that govern their fate. These stimuli encompass biochemical as well as biomechanical cues (shear, tensile, and compressive stresses) that are usually studied separately. The phosphatidylinositol 3-kinase (PI3K) enzymes, producing signaling phosphoinositides at plasma and intracellular membranes, are key in intracellular signaling and vesicular trafficking pathways. Recent evidence in cancer research demonstrates that these enzymes are essential in mechanotransduction. Despite this, the importance of the integration of biomechanical cues and PI3K-driven biochemical signals is underestimated. In this opinion article, we make the hypothesis that modeling of biomechanical cues is critical to understand PI3K oncogenicity. We also identify known/missing knowledge in terms of isoform specificity and molecular pathways of activation, knowledge that is needed for clinical applications.

[Alcohol consumption and head and neck cancer]. / Consommation d'alcool et cancers ORL.

Alcohol is often considered as a simple co-factor, potentiating the carcinogenic effect of tobacco, in head and neck cancer. However, its own effect is less clear. It has been recognized by the International Agency for Research on Cancer (IARC) as a risk factor for head and neck cancer for many years. It seems that the risk is a function of the importance of consumption, with certain genetic predispositions. This risk can also decrease if consumption stops, with a prolonged interruption. In addition, alcohol consumption may have a negative influence on the prognosis of patients with this type of cancer. A preventive action is therefore essential, among other things via information to the patient provided by health providers.

En cancérologie ORL, l'alcool est souvent considéré comme un simple co-facteur, potentialisant l'effet carcinogène du tabac. Son effet propre est moins clair. Il est pourtant reconnu par le Centre International de Recherche sur le Cancer (CIRC) comme un facteur de risque de cancer ORL depuis de nombreuses années. Il semble que le risque soit fonction de l'importance de la consommation, avec la contribution de certaines prédispositions génétiques. Ce risque peut également diminuer en cas d'arrêt de la consommation, moyennant un arrêt prolongé. Par ailleurs, la consommation d'alcool pourrait avoir une influence néfaste sur le pronostic des patients atteints de ces cancers. Une action préventive est donc primordiale, entre autres interventions, via l'information du patient par le corps médical.

Impact of bipolar disorder on eating disorders severity in real-life settings.

BACKGROUND: Comorbidity of bipolar disorder (BD) and eating disorders (ED) is common and increases the course and severity of BD. However, the impact of comorbid BD on the clinical profile of ED patients remains unclear. Most studies have focused on patients primarily assessed for BD and data on patients with a primary diagnosis of ED are sparse. We investigated the association between a dual diagnosis and severity in terms of clinical, neuropsychological dimensions and daily functioning. METHOD: Two hundred and sixty-one patients with ED were consecutively recruited. BD was screened with the MINI and further confirmed in the French expert centre network. The severity of ED symptoms was assessed with the EDE-Q and EDI-2, daily functioning with the FAST. The neurocognitive assessment targeted attention, set-shifting and decision-making. RESULTS: Forty-nine patients screened positive for BD, but diagnosis was confirmed in only thirty patients (11.5% of the cohort). After multiple adjustments, comorbidity was associated with greater severity on the total score and three subscales of the EDE-Q and on four of the ten dimensions of the EDI-2. Comorbid BD was associated with lower daily functioning but not with lower neuropsychological performance. LIMITATIONS: Sample referred to specialist clinics not large enough to authorize an analysis by subtype and cross-sectional evaluation. CONCLUSION: The association between ED and BD increases ED severity for most of these core features. It negatively impacts daily functioning. The results also highlight issues about the validity of screening tools to detect BD in patients with ED.

[Reappraisal of metformin : less restrictions and more potential indications]. / La metformine revisitée : moins de restrictions et davantage d'indications.

While commercialized since over 60 years, metformin is still the first-line drug recommended for the management of type 2 diabetes and is thus today the first glucose-lowering agent used worldwide. Despite this long experience, metformin retains its mysteries, especially regarding the underlying mechanisms responsible for its antidiabetic activity and other potential beneficial effects. During the last years, some contra-indications of metformin use have been at least partially withdrawn while new indications have been recognized. Furthermore, interesting prospects have been reported in important, although unexpected, medical areas such as cancer and neurodegenerative diseases. However, promising results in animal studies and observational human studies have now to be confirmed in well conducted randomized controlled trials.

Commercialisée depuis plus de 60 ans, la metformine est recommandée en première intention dans le traitement du diabète de type 2, ce qui en fait, aujourd'hui, le médicament anti-hyperglycémiant le plus prescrit à travers le monde. Malgré cette longue expérience, la metformine garde ses mystères, notamment quant aux mécanismes qui sous-tendent son action antidiabétique et d'autres effets potentiels. Au cours des dernières années, certaines contre-indications à l'utilisation de la metformine ont été, au moins partiellement, levées tandis que de nouvelles indications apparaissent avec, par ailleurs, des perspectives intéressantes dans des domaines aussi importants qu'inattendus, comme le cancer ou les maladies neurodégénératives. Les résultats prometteurs des études animales et des études observationnelles humaines doivent cependant être vérifiés dans des essais d'intervention contrôlés bien conduits.

Entanglement between more than two hundred macroscopic atomic ensembles in a solid.

There are both fundamental and practical motivations for studying whether quantum entanglement can exist in macroscopic systems. However, multiparty entanglement is generally fragile and difficult to quantify. Dicke states are multiparty entangled states where a single excitation is delocalized over many systems. Building on previous work on quantum memories for photons, we create a Dicke state in a solid by storing a single photon in a crystal that contains many large atomic ensembles with distinct resonance frequencies. The photon is re-emitted at a well-defined time due to an interference effect analogous to multi-slit diffraction. We derive a lower bound for the number of entangled ensembles based on the contrast of the interference and the single-photon character of the input, and we experimentally demonstrate entanglement between over two hundred ensembles, each containing a billion atoms. We also illustrate the fact that each individual ensemble contains further entanglement.Multipartite entanglement is of both fundamental and practical interest, but is notoriously difficult to witness and characterise. Here, Zarkeshian et al. demonstrate multipartite entanglement in an atomic frequency comb storing a single photon in a Dicke state spread over a macroscopic ensemble.

[Platypnea, orthodeoxia A report of two cases]. / Platypnée, orthodéoxie À propos de deux cas.

The plathypnea orthodeoxia syndrome is a rare condition that is characterized by dyspnea and hypoxia that occurs in the upright position and improves with recumbency. The diagnostic is often made tardively and requires the combination of two components: a mechanical one (for example a patent foramen ovale) and a kinetic one (for example COPD). This combination contributes to the blood flow through the communication. The treatment consists of closing the veno-arterial communication (in the case of a patent foramen ovale, the closing of the inter-atrial septum) (Knapper et al, 2014). In the present article, we describe two severe hypoxemic patients suffering from this syndrome. Both cases were associated with an acute pulmonary disease. A review of the literature is performed.

New in vivo model to analyse the expression of angiogenic genes in the borders of a cleft lip.

Defects in the fusion of facial buds can result from an anomaly in tissue development or apoptosis, or both. Our working hypothesis was that anomalies in the development of tissues could be caused by a genetic angiogenic defect. Our main objective was to design a reproducible experimental model to study the expression of angiogenic genes in the borders of cleft lips with or without cleft palate. We therefore prospectively studied seven non-syndromic patients, three with a cleft lip (2 right, 1 left), and four with a cleft lip and palate (1 bilateral, 2 right, 1 left), with no CGH (comparative genomic hybridisation) array, who had primary operations to repair their clefts. We also used four controls (cultured fibroblasts from healthy skin samples). The mean (range) age at operation was 44 (13-77) days. We studied the lateral and medial borders histologically and did qPCR (quantitative real-time polymerase chain reaction) analysis for gene expression with 22 genes of interest (and two housekeeping genes) involved in cleft lip and angiogenesis. The qPCR analysis found significant (p<0.05) overexpression of eight genes in the medial border and seven in the lateral border, and underexpression of nine genes in the medial, and ten in the lateral border. The difference in expression between the two borders was not significant. This preliminary study has enabled us to develop a new method to analyse the expression of angiogenic genes in the borders of cleft lips.

Tyrosine kinase inhibition is an important factor for gene expression of CRTH2 in human eosinophils and lymphocytes: A novel mechanism for explaining eosinophils recruitment by the neuro-immune axis in allergic rhinitis.

We recently shown a novel neuro-immune competition between vasoactive intestinal peptide (VIP) and PGD2 for CRTH2 receptor, and that genistein augmented VIP and PGD2-induced eosinophil chemotaxis. However, there are neither studies on the CRTH2 gene expression in allergic rhinitis (AR) nor in the effect of tyrosine kinase inhibitors in CRTH2 gene regulation. Our Objectives were to study the gene expression modulation of CRTH2 receptor in AR patients and the effect of tyrosine kinase inhibitors (TKIs) on CRTH2 gene modulation. Nasal provocation tests, ELISA, qRT-PCR, western blot, flow cytometry and chemotaxis assays in modified micro-Boyden chambers, were all used, to achieve our objectives. Herein we show that AR patients increased the amounts of VIP and PGD2 in their nasal secretions in the early phase reaction, however CRTH2 gene expression from leukocytes recovered in their nasal secretions was upregulated only during the late phase reaction. The TKIs; Genistein, Erbstatin and Herbimycin A, induced the gene expression of CRTH2 and increased the protein content of CRTH2 in both human lymphocytes and eosinophils. This was functional as PGD2/VIP-induced eosinophil chemotaxis was augmented by the TKIs and inhibited by pervanadate, the tyrosine phosphatase inhibitor. These results open channels for therapeutic modalities targeting CRTH2 molecules in AR.

Associations between adverse childhood experiences and clinical characteristics of eating disorders.

Patients with eating disorders (EDs) frequently report a history of childhood trauma (CT). We investigated whether certain subtypes of CT are associated with more severe features of EDs, independently of psychiatric comorbidity, and whether they act additively. One hundred and ninety-two patients with DSM-V-defined EDs were consecutively recruited. Five clinical characteristics were assessed: restraint, eating, shape and weight concerns on the EDE-Q, and daily functioning. CT was assessed by the childhood traumatism questionnaire. The clinical features were associated with at least one CT subtype (emotional, sexual or physical abuse, emotional neglect). Multivariate analyses adjusted for lifetime comorbid psychiatric disorders revealed that emotional abuse independently predicted higher eating, shape and weight concerns and lower daily functioning, whereas sexual and physical abuse independently predicted higher eating concern. A dose-effect relationship characterised the number of CT subtypes and the severity of the clinical features, suggesting a consistent and partly independent association between CT and more severe clinical and functional characteristics in EDs. Emotional abuse seems to have the most specific impact on ED symptoms. Last, not all CT subtypes have the same impact but they do act additively.

Is Serum Serotonin Involved in the Bone Loss of Young Females with Anorexia Nervosa?

Recent experimental data suggest that circulating serotonin interacts with bone metabolism, although this is less clear in humans. This study investigated whether serum serotonin interferes with bone metabolism in young women with anorexia nervosa (AN), a clinical model of energy deprivation. Serum serotonin, markers of bone turnover [osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), type I-C telopeptide breakdown products (CTX)], leptin, soluble leptin receptor (sOB-R), and insulin-like growth factor-1 (IGF-1) and its binding protein (IGFBP-3) were assessed. Whole body, spine, hip, and radius areal bone mineral density BMD (aBMD) were assessed by dual-energy X-ray absorptiometry in 21 patients with AN and 19 age-matched controls. Serum serotonin, leptin, IGF-1, IGFBP-3, OC, PINP, and aBMD at all sites, radius excepted, were significantly reduced in AN whereas CTX and sOB-R were increased compared with controls. Serum serotonin levels were positively correlated with weight, body mass index, whole body fat mass, leptin, and IGF-1, and negatively with CTX for the entire population. Low serum serotonin levels are observed in patients with AN. Although no direct link between low serum serotonin levels and bone mass was identified in these patients, the negative relationship between serotonin and markers of bone resorption found in all population nevertheless suggests the implication of serotonin in bone metabolism. Impact of low serum serotonin on bone in AN warrants further studies.

Evidence of a link between resting energy expenditure and bone remodelling, glucose homeostasis and adipokine variations in adolescent girls with anorexia nervosa.

UNLABELLED: Low bone mass is a consequence of anorexia nervosa (AN). This study assessed the effects of energy deficiency on various bone and hormonal parameters. The interrelationships between energy deficiency and bone remodelling, glucose homeostasis and adipokines underscore the importance of preventing energy deficiency to limit demineralisation and hormonal alterations in AN patients. INTRODUCTION: Low areal bone mineral density (aBMD) is a well-known consequence of AN. However, the impact of reduced energy expenditure on bone metabolism is unknown. This study assessed the effects of energy deficiency on bone remodelling and its potential interactions with glucose homeostasis and adipose tissue-derived hormones in AN, a clinical model for reduced energy expenditure. METHODS: Fifty women with AN and 50 age-matched controls (mean age 18.1 ± 2.7 and 18.0 ± 2.1 years, respectively) were enrolled. aBMD was determined with DXA. Resting energy expenditure (REEm), a marker of energy status, was indirectly assessed by calorimetry. Bone turnover markers, undercarboxylated osteocalcin (ucOC), parameters of glucose homeostasis, adipokines and growth factors were concomitantly evaluated. RESULTS: AN patients presented low aBMD at all bone sites. REEm, bone formation markers, ucOC, glucose, insulin, HOMA-IR, leptin and IGF-1 were significantly reduced, whereas the bone resorption marker, leptin receptor (sOB-R) and adiponectin were elevated in AN compared with CON. In AN patients, REEm was positively correlated with weight, BMI, whole body (WB) fat mass, WB fat-free soft tissue, markers of bone formation, glucose, insulin, HOMA-IR, leptin and IGF-1 and negatively correlated with the bone resorption marker and sOB-R. Biological parameters, aBMD excepted, appeared more affected by the weight variation in the last 6 months than by the disease duration. CONCLUSIONS: The strong interrelationships between REEm and bone remodelling, glucose homeostasis and adipokines underscore the importance of preventing energy deficiency to limit short- and long-term bone demineralisation and hormonal alterations in AN patients.

[Clinical approach of a suspicion of hypoglycaemic malaise in a nondiabetic adult]. / La vignette diagnostique de l'étudiant Mise au point d'une suspicion de malaise hypoglycémique chez une personne adulte non diabétique.

Malaises are often attributed to hypoglycaemia in nondiabetic people who don't have any other serious medical problem. However, such a diagnosis is often overused, because not really demonstrated in most instances. The diagnosis of hypoglycaemia should be structured, based upon the Whipple triad. First, the anamnesis must search for adrenergic and neuroglucopenic symptoms that suggest hypoglycaemia. Afterwards, hypoglycaemia must be authentified by a measurement of a low glucose level at the time of a malaise. Finally, if the malaise is due to a hypoglycaemia, it should resume rapidly after the administration of sugar. When the diagnosis is made based upon this triad, the medical interview should precise the severity of the symptoms and focus on the chronology of the malaises, after meal or in the fasting state, which is crucial to differentiate functional reactice hypoglycaemia from hypoglycaemia due to an insulinoma. Finally, additional medical examinations may be performed, first based upon clinical biology followed, if necessary, by medical imaging. They will not only confirm the diagnosis of hypoglycaemia, but also contribute to find the cause of hypoglycaemia, which will help in choosing the therapeutic strategy.

Résumé : La survenue de malaises est souvent attribuée à une hypoglycémie chez des personnes non diabétiques et, a priori, sans autre problème de santé. Ce diagnostic est, cependant, souvent galvaudé, car habituellement non clairement démontré. Le diagnostic d'hypoglycémie doit se faire de façon structurée en se basant sur la triade de Whipple. Tout d'abord, l'anamnèse doit rechercher les symptômes évocateurs d'hypoglycémie, adrénergiques et neuroglucopéniques. Ensuite, l'hypoglycémie doit être authentifiée par une mesure d'une valeur basse au moment d'un malaise. Enfin, s'il s'agit bien d'une hypoglycémie, le malaise doit disparaître rapidement après resucrage. Une fois le diagnostic posé sur la base de cette triade, l'anamnèse doit faire préciser, outre la sévérité des malaises, leur chronologie, après les repas ou à jeun, ce qui oriente vers une hypoglycémie réactive, fonctionnelle, ou vers une hypoglycémie d'origine organique (insulinome). Des examens complémentaires, faisant d'abord appel à la biologie clinique, ensuite éventuellement à l'imagerie médicale, permettront de, non seulement confirmer le diagnostic d'hypoglycémie, mais aussi d'en préciser l'origine, ce qui orientera la stratégie thérapeutique.

Comparison of viscoelastic property characterization of plastisol phantoms with magnetic resonance elastography and high-frequency rheometry.

This study aims at evaluating Magnetic Resonance Elastography (MRE) as a reliable technique for the characterization of viscoelastic properties of soft tissues. Three phantoms with different concentrations of plastisol and softener were prepared in order to mechanically mimic a broad panel of healthy and pathological soft tissues. Once placed in a MRI device, each sample was excited by a homemade external driver, inducing shear waves within the medium. The storage (G') and loss (G") moduli of each phantom were then reconstructed from MRE acquisitions over a frequency range from 300 to 1,000 Hz, by applying a 2D Helmholtz inversion algorithm. At the same time, mechanical tests were performed on four samples of each phantom with a High-Frequency piezo-Rheometer (HFR) over an overlapping frequency range (from 160 to 630 Hz) with the same test conditions (temperature, ageing). The comparison between both techniques shows a good agreement in the measurement of the storage and loss moduli, underlying the capability of MRE to noninvasively assess the complex shear modulus G* of a medium and its interest for investigating the viscoelastic properties of living tissues. Moreover, the phantoms with varying concentrations of plastisol used in this study show interesting rheological properties, which make them good candidates to simulate the broad variety of viscoelastic behaviors of healthy and pathological soft tissues.

Transport of indirect excitons in ZnO quantum wells.

We report on spatially- and time-resolved emission measurements and observation of transport of indirect excitons in ZnO/MgZnO wide single quantum wells.

Frequency and prognostic value of cutaneous molecular residual disease in mycosis fungoides: a prospective multicentre trial of the Cutaneous Lymphoma French Study Group.

BACKGROUND: Monoclonal T-cell receptor (TCR) rearrangement is detected in 57-75% of early-stage mycosis fungoides (MF) at diagnosis. A retrospective study showed molecular residual disease (MRD) in 31% of patients in complete clinical remission (CR) after 1 year of treatment. OBJECTIVES: To confirm the frequency of MRD at 1 year and to determine its prognostic value for further relapse. METHODS: Patients with T1-, T2- or T4-stage MF were prospectively included in this multicentre study. At diagnosis, clinical lesions and healthy skin were biopsied. After 1 year of topical treatment, previously involved skin of patients in CR was biopsied for histology and analysis of TCR-γ gene rearrangement. The results were compared with the clinical status each year for 4 years. RESULTS: We included 214 patients, 133 at T1, 78 at T2 and three at T4 stage. At diagnosis, 126 of 204 cases (61·8%) showed TCR clonality in lesional skin. After 1 year, 83 of 178 patients (46·6%) still being followed up were in CR and 13 of 63 (21%) showed MRD. At 4 years, 55 of 109 patients (50·5%) still being followed up were in CR and 44 of 109 (40·4%) were in T1 stage. MRD did not affect clinical status at 4 years (CR vs. T1/T2, P = 1·0; positive predictive value 36·4%; negative predictive value 67·6%). CONCLUSIONS: T-cell clonality at diagnosis and MRD at 1 year are not prognostic factors of clinical status at 4 years.

The neuron-derived orphan receptor 1 (NOR1) is induced upon human alternative macrophage polarization and stimulates the expression of markers of the M2 phenotype.

BACKGROUND: Atherosclerosis is an inflammatory disease in which macrophages play a crucial role. Macrophages are present in different phenotypes, with at the extremes of the spectrum the classical M1 pro-inflammatory and the alternative M2 anti-inflammatory macrophages. The neuron-derived orphan receptor 1 (NOR1), together with Nur77 and Nurr1, are members of the NR4A orphan nuclear receptor family, expressed in human atherosclerotic lesion macrophages. However, the role of NOR1 in human macrophages has not been studied yet. OBJECTIVES: To determine the expression and the functions of NOR1 in human alternative macrophages. METHODS AND RESULTS: In vitro IL-4 polarization of primary monocytes into alternative M2 macrophages enhances NOR1 expression in human but not in mouse macrophages. Moreover, NOR1 expression is most abundant in CD68+MR+ alternative macrophage-enriched areas of human atherosclerotic plaques in vivo. Silencing NOR1 in human alternative macrophages decreases the expression of several M2 markers such as the Mannose Receptor (MR), Interleukin-1 Receptor antagonist (IL-1Ra), CD200 Receptor (CD200R), coagulation factor XIII A1 polypeptide (F13A1), Interleukin 10 (IL-10) and the Peroxisome Proliferator-Activated Receptor (PPAR)γ. Bioinformatical analysis identified F13A1, IL-1Ra, IL-10 and the Matrix Metalloproteinase-9 (MMP9) as potential target genes of NOR1 in human alternative macrophages. Moreover, expression and enzymatic activity of MMP9 are induced by silencing and repressed by NOR1 overexpression in M2 macrophages. CONCLUSIONS: These data identify NOR1 as a transcription factor induced during alternative differentiation of human macrophages and demonstrate that NOR1 modifies the alternative macrophage phenotype.