Human papillomavirus (HPV) vaccination: What can be found on the Web? Qualitative analysis of the Doctissimo.fr forum data.

BACKGROUND: Vaccine hesitancy is a major issue in general practice. Regarding human papillomavirus, less than 20% of young French girls are vaccinated. With widespread availability of health information, the Internet seems to be a place of choice to discuss this reluctance. The main objective of this study was to explore perceptions of human papillomavirus vaccination through an analysis of the Doctissimo.fr forum data. METHODS: Using Nvivo software, a qualitative study was carried out from October 2017 to May 2018 on the Doctissimo.fr discussion forum. Online discussion threads not having any message since 2010 were excluded. All threads were analyzed by two independent evaluators. RESULTS: Faced with the doubt that emanated from the discussions and the confusion about the role of the vaccine, Internet users used multiple references in order to develop a reliable discourse. The general practitioner remained a trusted person. While the vaccine was perceived as risky, the cervical smear was approved and encouraged. Although the vaccine remained a feminine concern, males also entered this debate. Through their shared experiences, Internet users tried to influence others about whether or not to get vaccinated. CONCLUSION: Changing the sexual image of the vaccine could help to establish a collective vaccination policy. Public health policies play an essential role by working with general practitioners and by increasing visibility on the web. The usefulness of the vaccine in 2019 seems to be questioned by Internet users as shown by their major approval of cervical smears. However, these two methods remain complementary in the fight against cervical cancer.

Field-testing the new anaphylaxis' classification for the WHO International Classification of Diseases-11 revision.

BACKGROUND: To consolidate the new classification model addressed to the allergic and hypersensitivity conditions according to the International Classification of Diseases (ICD)-11 revision timeline, we here propose real-life application of quality assurance methodology to evaluate sensitivity and accuracy of the 'Anaphylaxis' subsection. METHODS: We applied field-testing methodology by analysing all the consecutive inpatients' files documented as allergies from the University Hospital of Montpellier electronic database for the period of 1 year. The files clinically validated as being anaphylaxis were manually blind-coded under ICD-10 and current ICD-11 beta draft. The correspondence of coding and the impressions regarding sensibility were evaluated. RESULTS: From all 2318 files related to allergic or hypersensitivity conditions, 673 had some of the anaphylaxis ICD-10 codes; 309 files (46%) from 209 patients had anaphylaxis and allergic or hypersensitivity comorbidities description. The correspondence between the two coders was perfect for 162 codes from all 309 entities (52.4%) (Cohen-kappa value 0.63) with the ICD-10 and for 221 codes (71.5%) (Cohen-kappa value 0.77) with the ICD-11. There was a high agreement regarding sensibility of the ICD-11 usability (Cohen-kappa value 0.75). CONCLUSION: We here propose the first attempt of real-life application to validate the new ICD-11 'Anaphylaxis' subsection. Clearer was the improvement in accuracy reaching 71.5% of agreement when ICD-11 was used. By allowing all the relevant diagnostic terms for anaphylaxis to be included into the ICD-11 framework, WHO has recognized their importance not only to clinicians but also to epidemiologists, statisticians, healthcare planners and other stakeholders.

Intention to get vaccinations against COVID-19 in French healthcare workers during the first pandemic wave: a cross-sectional survey.

BACKGROUND: Healthcare workers (HCWs) are at the frontline of the COVID-19 pandemic and identified as a priority target group for COVID-19 vaccines. We aimed to determine COVID-19 vaccine acceptance rate in HCWs in France. METHODS: We conducted an anonymous survey from 26th March to 2nd July 2020. The primary endpoint was the intention to get vaccinated against COVID-19 if a vaccine was available. RESULTS: Two-thousand and forty-seven HCWs answered the survey; women accounted for 74% of respondents. Among respondents, 1.554 (76.9%, 95% confidence interval 75.1-78.9) would accept a COVID-19 vaccine. Older age, male gender, fear about COVID-19, individual perceived risk and flu vaccination during previous season were associated with hypothetical COVID-19 vaccine acceptance. Nurses and assistant nurses were less prone to accept vaccination against COVID-19 than physicians. Vaccine hesitancy was associated with a decrease in COVID-19 vaccine acceptance. Flu vaccine rate was 57.3% during the previous season, and 54.6% of the respondents had the intention to get a flu vaccine during the next season. CONCLUSIONS: Intention to get vaccinated against COVID-19 reached 75% in HCWs with discrepancies between occupational categories. COVID-19 pandemic had no positive effect on flu vaccine acceptance rate.

Patient decision aid in vaccination: a systematic review of the literature.

INTRODUCTION: Decision-making for patients and their families in the field of vaccination is difficult, involving many multidimensional factors. The complexity of this process is directly responsible for the phenomenon of vaccine hesitancy. Decision aids are instruments that provide information on a specific subject, explaining the advantages and disadvantages of a decision in a personalized way, thus clarifying the patient's values. AREAS COVERED: A systematic review using PRISMA guidelines was conducted to carry out an inventory of decision aids in the field of vaccination and assess their impact on vaccine coverage and decisional conflict. EXPERT OPINION: Decision aids reduce decision-making conflict and could be good tools to address the phenomenon of vaccine hesitancy. It seems essential to integrate health professionals and patients into the design of future decision aids. This would simplify the use of these tools during the consultation. However, their effect on vaccine coverage remains uncertain. Further studies seem necessary in order to conclude that vaccination coverage is effective.

The human colonic microflora influences the alterations of xenobiotic-metabolizing enzymes by catechins in male F344 rats.

As other xenobiotics, polyphenols are metabolized both by the endogenous detoxication system and the gut microflora. We hypothesized that the presence of a gut microflora may account for the effect of catechins on phase I and II xenobiotic-metabolizing enzymes and that the human bacterial metabolites may be different from those of a rodent gut microflora. Therefore, the effects of 2% (+)-catechin or 2% (-)-epicatechin were studied in germ free (GF) rats and rats inoculated with the flora of a human volunteer (HFA). In addition, the catechins were administered in ethanol as a vehicle. In the liver, (+)-catechin or (-)-epicatechin decreased the total amount of CYP450 in both GF and HFA rats while the isoenzyme CYP2E1 decreased. In GF rats only, CYP2C11 increased when compared to the rats treated with the vehicle alone. (+)-catechin increased the specific activity of UGT-chloramphenicol in GF rats only and that of cytosolic glutathion-S-transferase (GST) in HFA rats only. In the intestine, (+)-catechin and (-)-epicatechin increased the specific activity of UGT-4-methylumbelliferone in both GF and HFA rats and that of UGT- chloramphenicol in HFA rats only. In conclusion, the presence of a human flora in rats is able to modify the inducing effect of catechins on the UGT and GST activities suggesting the involvement of bacterial metabolites. The alterations on CYP 450 are independent of the presence of a human gut flora.

[Epidermoid cancer of the kidney pelvis]. / Cancer épidermoïde du bassinet.

Squamous cell carcinoma of the renal pelvis is a rare tumour, mainly occurring in elderly patients with neglected and secondarily infected pyelocaliceal stones. It has a poor prognosis. The authors report the case of a 74-year old man with a destroyed and painful kidney containing a staghorn calculus for 30 years. The preoperative diagnosis was pyonephrosis, but nephrectomy, justified by the symptoms, showed that the kidney was invaded by a squamous cell carcinoma of the renal pelvis invading the psoas. The patient died 1 month after the operation. Treatment is essentially preventive by removal of staghorn calculi and management of chronic urinary tract infections.

D-glyceraldehyde-3-phosphate dehydrogenase from HeLa cells--1. Purification and properties of the enzyme.

1. D-GPDH from HeLa cells was isolated and purified. 2. Some basic kinetic constants are reported. 3. Sodium dodecyl polyacrylamide gel electrophoresis gave a single band with a molecular weight of approximately 36 K. 4. ATP and NADH inhibit competitively enzyme activity. 5. Comparative catalytic properties of GPDH from normal and tumor cells were effectuated.

D-glyceraldehyde-3-phosphate dehydrogenase from HeLa cells--2. Immunological characterization.

1. An immunological relationship between GPDH from HeLa cells and those from other phylogenetically different sources was carried out. 2. It was found that HeLa cell anti-GPDH antibody presented an immunological cross-reaction specificity with GPDH from HeLa cells, Caiman sp. muscle and human mammary tumor tissue and a partial one with GPDH from Anas sp. muscle.

Prevention of graft-versus-host disease in mice using a suicide gene expressed in T lymphocytes.

Alloreactive T cells present in a bone marrow transplant are responsible for graft-versus-host disease (GVHD), but their depletion is associated with impaired engraftment, immunosuppression, and loss of the graft-versus-leukemia effect. We developed a therapeutic strategy against GVHD based on the selective destruction of these alloreactive T cells, while preserving a competent T-cell pool of donor origin. We generated transgenic mice expressing in their T lymphocytes the Herpes simplex type 1 thymidine kinase (TK) suicide gene that allows the destruction of dividing T cells by a ganciclovir treatment. T cells expressing the TK transgene were used to generate GVHD in irradiated bone marrow grafted mice. We show that a short 7-day ganciclovir treatment, initiated at the time of bone marrow transplantation, efficiently prevented GVHD in mice receiving TK-expressing T cells. These mice were healthy and had a normal survival. They maintained a T-cell pool of donor origin that responded normally to in vitro stimulation with mitogens or third party alloantigens, but were tolerant to recipient alloantigens. Our experimental system provides the proof of concept for a therapeutic strategy of GVHD prevention using genetically engineered T cells.

Effect of combined cytostatic cyclosporin A and cytolytic suicide gene therapy on the prevention of experimental graft-versus-host disease.

The immunosuppressive drug cyclosporin A (CsA) represents the standard preventive treatment of graft-versus-host disease (GVHD), the main complication of allogeneic hematopoietic stem cell transplantation (HSCT). However, its efficacy is only partial and many patients develop lethal GVHD despite CsA. A strategy of genetic immunosuppression based on conditional elimination of donor T cells expressing the Herpes simplex type 1 thymidine kinase (TK) suicide gene was recently developed. In this system, ganciclovir (GCV) selectively kills dividing but not quiescent TK T cells. Since CsA is known to have a cytostatic effect on T cells, it could negatively interfere with the division-dependent TK gene therapy. We thus tested whether administration of CsA would antagonize elimination of alloreactive donor TK T cells mediated by GCV in a murine model of GVHD. In vivo experiments revealed that, contrary to GCV, CsA only transiently controlled alloactivation-induced T cell proliferation, and likewise could not prevent lethal GVHD. When T cells resumed proliferation under CsA, they were however still sensitive to GCV. Survival, as well as immune reconstitution, was excellent in mice treated with GCV alone or in combination with CsA. These observations should help to design improved suicide gene therapy trials in the field of allogeneic HSCT.

Position-dependent variegation of a CD4 minigene with targeted expression to mature CD4+ T cells.

The CD4 gene follows a complex and highly regulated pattern of expression throughout T cell development. This expression is governed by different regulatory elements that have been partly identified, including a promoter, a proximal enhancer, and a silencer. Here we show that a CD4 minigene comprising a combination of these elements is specifically expressed in mature CD4+ T cells of transgenic mice, but not in CD4+CD8+ double positive thymocytes. The proportion of transgene-expressing CD4+ T cells was constant within a given transgenic line, but varied greatly from one line to another. We demonstrate that this pattern of expression is due to integration of the transgene within or in the vicinity of centromeric heterochromatin. This position-effect variegation demonstrated with a short CD4 transgene has not been observed with larger ones containing additional regulatory sequences, suggesting that the CD4 gene contains a locus control region. Such position-dependent effects must be taken into consideration when developing transgenic models or gene transfer vectors because they can result in the absence of transgene expression in a subpopulation of target cells. Finally, the combination of the CD4 gene silencer, proximal enhancer, and promoter provides an interesting tool to selectively express genes of interest in mature CD4+ T cells of transgenic mice and for the development of gene therapy vectors.

Fertile homozygous transgenic mice expressing a functional truncated herpes simplex thymidine kinase delta TK gene.

Dividing cells expressing the Herpes simplex type 1 thymidine kinase (TK) can be killed upon ganciclovir treatment. Likewise, conditional cell knock-out can be obtained in transgenic mice expressing a TK gene placed under the control of tissue-specific regulatory sequences. Such animals provide powerful experimental systems for assessing the functional role of specific cell populations through their time-controlled ablation. However, whatever the regulatory sequences used, a leaky toxic overexpression of TK in testis renders male TK-transgenic mice sterile and prevents the generation of homozygous TK-expressing animals. To solve this problem, we designed a truncated TK variant (delta TK) not expressed in the testis. We generated transgenic mice expressing delta TK under the control of lymphocyte-specific regulatory sequences derived from the CD4 gene. The delta TK protein expressed in T-lymphocytes allowed the conditional ablation of activated T-cells in vitro and in vivo. Importantly, for one transgenic line we could generate fertile homozygous mice harboring a functional delta TK transgene. delta TK should thus dramatically facilitate the development of transgenic mice expressing a conditional suicide gene.