The Wood equation allows consistent fitting of individual antibody-response profiles of Zika virus or SARS-CoV-2 infected patients.

Antibody kinetic curves obtained during a viral infection are often fitted using aggregated patient data, hiding the heterogeneity of individual humoral immune responses. Individual antibody responses can be modeled using the Wood equation and grouped according to their profile. Such modeling takes into account several important kinetic parameters, such as the day when antibody detection becomes positive [daypos], the day of the maximal response [daymax], the maximum antibody level [levelmax], and the day when antibody detection becomes negative [dayneg]. Potential associations between these profiles and studied factors can then be tested.

Experiences of parents and caregivers in pediatric intensive care units: A qualitative study.

BACKGROUND: In pediatric intensive care units (PICUs), parents and healthcare professionals attend to children who verbally and non-verbally express their pain and suffering, fears, anxieties, desires, and wishes in complex intensive care situations. What can we learn from these experiences to improve the way we can take care of and support children? OBJECTIVES: The main objective of this clinical ethics study was to focus on the experience stories of parents during their child's hospitalization in a PICU, to analyze their discourse, and to propose an ethical perspective. METHOD: The current research collects the experience reports of parents during their child's hospitalization in a PICU and those of the caregivers who treated them. A total of 17 semi-directive interviews were conducted in the PICU of the Nantes University Hospital from November 2017 to June 2019. Each interview lasted around 1 h. The main results of our study are analyzed and informed by the four ethical principles of T. Beauchamp and J. Childress: autonomy, beneficence, non-maleficence, and justice. RESULTS: The interviews highlighted the difficulties encountered by parents during the hospitalization of their children, such as the distance between their home and the hospital, the technicality of PICU environment, and the difficulty in finding their place as parents. For medical and paramedical teams, their main concerns are undoubtedly to improve the coherence and continuity of their stand toward parents, to promote parental autonomy, and to remain fully aware of the profound existential changes that the child's illness brings about for parents: It is the caregivers' duty to take this into account and to respect the parents' rhythm as much as possible. CONCLUSIONS: The main disagreements between healthcare teams and parents, where they exist, are communication problems that are easily controlled, for the most part, by caregivers.

Peripherally inserted central catheters: a hidden emerging cause of infection outbreaks.

In our institution, between January 2010 and December 2017, 15 140 peripherally inserted central catheters (PICCs) were inserted in 12 314 patients. Using time-series analysis to evaluate the annual historical trend (AHT), we observed a significant increase in bloodstream infections (BSIs; AHT = 24; p < 0.001) and associated deaths (AHT = 3; p 0.02) in patient with PICCs. The risk of experiencing a BSI was significantly higher in patients with PICCs (odds ratio = 9.6; 95% confidence interval, 9.08-10.18; p < 0.001). To reduce PICC-related BSIs and their related mortality, it is important to limit the overuse of PICCs and to implement a 'no PICC' policy by limiting the insertion of PICCs to situations without other available options.

Assessment of VITEK® MS IVD database V3.0 for identification of Nocardia spp. using two culture media and comparing direct smear and protein extraction procedures.

We assessed the performance of the VITEK® MS IVD V3.0 matrix-assisted laser desorption ionization - time of flight mass spectrometry (MALDI-ToF MS) V3.0 database for the identification of Nocardia spp. as compared with targeted DNA sequencing. A collection of 222 DNA sequence-defined Nocardia spp. strains encompassing 18 different species present or not in the database was tested. Bromocresol purple agar (BCP) and Columbia agar +5% sheep's blood (COS) culture media were used together with two different preparation steps: direct smear and a "3 attempts" procedure that covered (1) spotting of an extract, (2) new spotting of the same extract, and (3) spotting of a new extract. The direct smear protocol yielded low correct identification rates (≤ 15% for both media) whereas protein extraction yielded correct identification results (> 67% regardless of the media used.). The use of 2 additional attempts using repeat or new extracts increased correct identification rates to 87% and 91% for BCP and COS, respectively. When using the 3 attempts procedure, the best identification results, independent of media types, were obtained for N. farcinica and N. cyriacigeorgica (100%). Identification attempts 2 and 3 allowed to increase the number of correct identifications (BCP, +20%; COS, +13%). The enhancement in performance during attempts 2 and 3 was remarkable for N. abscessus (81% for both media) and low prevalence species (BCP, 70%; COS, 85%). Up to 3.4% and 2.4% of the strains belonging to species present in the database were misidentified with BCP and COS media, respectively. In 1.9% of the cases for BCP and 1.4% for COS, these misidentifications concerned a species belonging to the same phylogenetic complex. Concerning strains that are not claimed in the V3.0 database, N. puris and N. goodfellowi generated "No identification" results and 100% of the strains belonging to N. arthritidis, N.cerradoensis, and N. altamirensis yielded a misidentification within the same phylogenetic complex. Vitek® MS IVD V3.0 is an accurate and useful tool for identification of Nocardia spp.

Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids.

The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.

Emergence of Clostridium difficile tcdC variant 078 in Marseille, France.

The purpose of this investigation was to evaluate the epidemiology of hypervirulent Clostridium difficile ribotypes from January 2013 to February 2017 in the Marseille area of southern France. By using the Xpert Clostridium difficile Epi polymerase chain reaction (PCR) assay and sequencing the tcdC gene, we characterised C. difficile isolates from symptomatic patients diagnosed with C. difficile infection (CDI) in Marseille university hospitals. We first tested retrospectively 278 C. difficile samples isolated from January 2013 to December 2014 and observed a high prevalence of isolates with tcdC mutations and deletions previously described in both hypervirulent ribotypes RT027 and RT078 (16.4% and 10.7%, respectively). We highlighted the co-circulation of these two hypervirulent C. difficile tcdC variants (tV) with distinct epidemiological characteristics. While an RT027 outbreak occurred mainly as healthcare-associated infection in the elderly, CDI caused by tV078 occurred mainly in a younger population as community-associated infection. From January 2016, a systematic survey of these two hypervirulent C. difficile ribotypes revealed the emergence of CDI caused by tV078, currently being more prevalent than RT027 in the Marseille area. The present study is the first report of the emergence of CDI caused by tV078 in southern France. We showed the simultaneous circulation and sequential spread of hypervirulent ribotypes, such as RT027 and tV078. This emphasises the need for an efficient surveillance system for CDI with ribotyping and an optimised management of CDI caused by hypervirulent strains.

A colorimetric nanosensor based on a selective target-responsive aptamer kissing complex.

Herein, we report a novel approach for the design of a colorimetric aptasensor based on functionalized gold nanoparticle probes. This approach relies on the conjugation of nanoparticles by two functional DNA and RNA hairpins that engage specific kissing (loop-loop) interactions in response to the addition of a small analyte ligand, leading to particle aggregation and then red-to-purple colour change of the colloidal solution.

Description of 'Gorbachella massiliensis' gen. nov., sp. nov., 'Fenollaria timonensis' sp. nov., 'Intestinimonas timonensis' sp. nov. and 'Collinsella ihuae' sp. nov. isolated from healthy fresh stools with culturomics.

We report here the main characteristics of 'Gorbachella massiliensis' GD7T gen. nov., sp. nov., 'Fenollaria timonensis' GD5T sp. nov., 'Intestinimonas timonensis' GD4T sp. nov., and 'Collinsella ihuae' sp. nov. GD8T isolated from one fresh stool of a French volunteer. We used a bacterial culturomics approach combined with taxono-genomics.

'Bittarella massiliensis' gen. nov., sp. nov. isolated by culturomics from the gut of a healthy 28-year-old man.

We report here the main features of the proposed new bacterial genus Bittarella. The type strain 'Bittarella massiliensis' GD6T (CSUR P2149) was isolated from a stool sample from a healthy French man.

Imaging of postoperative complications following surgery for lung cancer.

The complications following surgery for lung cancer vary depending upon the comorbidities and the type of surgery. Hemorrhage, infections and pulmonary edemas are not specific to the type of resection but frequently occur following pneumonectomies. Morbidity following pneumonectomies is related to the significant changes in the contents of the intrathoracic space. Pulmonary infarction and torsion are emergency situations that develop following lobectomy. CT shows features of localized congestion and stenosis or occlusion of a vein or bronchus. Rapid identification of severe events, in particular by systematic CT is essential for appropriate management of a postoperative or delayed complication of lung cancer surgery.

"Intestinimonas massiliensis" sp. nov, a new bacterium isolated from human gut.

Here we report the main features of the proposed new bacterial species "Intestinimonas massiliensis" sp. nov. The type strain GD2T (CSUR = P1930) was isolated from the gut microbiota of a healthy patient using a culturomics approach combined with taxonogenomics.

Description of Clostridium phoceensis sp. nov., a new species within the genus Clostridium.

Clostridium phoceensis sp. nov., strain GD3T (= CSUR P1929 = DSM 100334) is the type strain of C. phoceensis sp. nov., a new species within the genus Clostridium. This strain was isolated from the gut microbiota of a 28-year-old healthy French man. C. phoceensis is a Gram-negative, spore-forming, nonmotile, strictly anaerobic bacterium. We describe its complete genome sequence and annotation, together with its phenotypic characteristics.

Normal postoperative appearances of lung cancer.

The major lung resections are the pneumonectomies and lobectomies. The sublobar resections are segmentectomies and wedge resections. These are performed either through open surgery through a thoracotomy or by video-assisted mini-invasive surgery for lobectomies and sublobar resections. Understanding the procedures involved allows the normal postoperative appearances to be interpreted and these normal anatomical changes to be distinguished from potential postoperative complications. Surgery results in a more or less extensive physiological adaptation of the chest cavity depending on the lung volume, which has been resected. This adaptation evolves during the initial months postoperatively. Chest radiography and computed tomography can show narrowing of the intercostal spaces, a rise of the diaphragm and shift of the mediastinum on the side concerned following major resections.

TLR9 re-expression in cancer cells extends the S-phase and stabilizes p16(INK4a) protein expression.

Toll-like receptor 9 (TLR9) recognizes bacterial, viral or cell damage-associated DNA, which initiates innate immune responses. We have previously shown that TLR9 expression is downregulated in several viral induced cancers including HPV16-induced cervical neoplasia. Findings supported that downregulation of TLR9 expression is involved in loss of anti-viral innate immunity allowing an efficient viral replication. Here we investigated the role of TLR9 in altering the growth of transformed epithelial cells. Re-introducing TLR9 under the control of an exogenous promoter in cervical or head and neck cancer patient-derived cells reduced cell proliferation, colony formation and prevented independent growth of cells under soft agar. Neither TLR3, 7, nor the TLR adapter protein MyD88 expression had any effect on cell proliferation, indicating that TLR9 has a unique role in controlling cell growth. The reduction of cell growth was not due to apoptosis or necrosis, yet we observed that cells expressing TLR9 were slower in entering the S-phase of the cell cycle. Microarray-based gene expression profiling analysis highlighted a strong interferon (IFN) signature in TLR9-expressing head and neck cancer cells, with an increase in IFN-type I and IL-29 expression (IFN-type III), yet neither IFN-type I nor IL-29 production was responsible for the block in cell growth. We observed that the protein half-life of p16(INK4a) was increased in TLR9-expressing cells. Taken together, these data show for the first time that TLR9 affects the cell cycle by regulating p16(INK4a) post-translational modifications and highlights the role of TLR9 in the events that lead to carcinogenesis.

Drancourtella massiliensis gen. nov., sp. nov. isolated from fresh healthy human faecal sample from South France.

Strain GD1(T) gen. nov., sp. nov., is the type strain of the newly proposed genus and species Drancourtella massiliensis, belonging to the Clostridiales order. This strain, isolated from the stool of a healthy person, is a Gram-positive rod, oxygen intolerant and nonmotile, with spore-forming activity. The features of this organism and its genome sequence are described. The draft genome is 3 057 334 bp long with 45.24% G + C content; it contains 2861 protein-coding genes and 64 RNA genes.

Multigene testing of moderate-risk genes: be mindful of the missense.

BACKGROUND: Moderate-risk genes have not been extensively studied, and missense substitutions in them are generally returned to patients as variants of uncertain significance lacking clearly defined risk estimates. The fraction of early-onset breast cancer cases carrying moderate-risk genotypes and quantitative methods for flagging variants for further analysis have not been established. METHODS: We evaluated rare missense substitutions identified from a mutation screen of ATM, CHEK2, MRE11A, RAD50, NBN, RAD51, RINT1, XRCC2 and BARD1 in 1297 cases of early-onset breast cancer and 1121 controls via scores from Align-Grantham Variation Grantham Deviation (GVGD), combined annotation dependent depletion (CADD), multivariate analysis of protein polymorphism (MAPP) and PolyPhen-2. We also evaluated subjects by polygenotype from 18 breast cancer risk SNPs. From these analyses, we estimated the fraction of cases and controls that reach a breast cancer OR≥2.5 threshold. RESULTS: Analysis of mutation screening data from the nine genes revealed that 7.5% of cases and 2.4% of controls were carriers of at least one rare variant with an average OR≥2.5. 2.1% of cases and 1.2% of controls had a polygenotype with an average OR≥2.5. CONCLUSIONS: Among early-onset breast cancer cases, 9.6% had a genotype associated with an increased risk sufficient to affect clinical management recommendations. Over two-thirds of variants conferring this level of risk were rare missense substitutions in moderate-risk genes. Placement in the estimated OR≥2.5 group by at least two of these missense analysis programs should be used to prioritise variants for further study. Panel testing often creates more heat than light; quantitative approaches to variant prioritisation and classification may facilitate more efficient clinical classification of variants.

Medical management of failed back surgery syndrome in Europe: evaluation modalities and treatment proposals.

Failed back surgery syndrome (FBSS) is defined as persistent pain more than 3 months after any form of spinal surgery. Due to its multifactorial origin, FBSS is often difficult to treat. In this context of failed back surgery, a very thorough assessment must be conducted concerning the site and characteristics of the pain (nociceptive or neuropathic), its mode of onset (presence or absence of pain-free intervals), and its impact on the patient's work and social life. Physical examination must exclude a non-spinal cause for the pain. MRI is the imaging modality of choice in this disease, but is often difficult to interpret, as MR signals are modified for 6 months after the operation. Scar tissue, which can be distinguished from recurrent disc hernia by its gadolinium enhancement, is present even in asymptomatic patients. After having eliminated infection and sacroiliac or posterior facet joint disease, the main aetiologies investigated are foraminal stenosis, degenerative disc disease, recurrent disc hernia, and non-union of spinal fusion; sometimes patients only experience persistent neuropathic pain. The treatment of failed back surgery syndrome with a predominant neuropathic component is based on the use of analgesics, especially antiepileptics, antidepressants or transcutaneous electrical stimulation. Epidural spinal infiltration should be considered as second-line treatment in view of the risk of serious neurological complications. Management must be based on a global, multidisciplinary approach with identification of any cognitive or behavioural disorders in combination with an appropriate functional rehabilitation programme.

Multicolumn spinal cord stimulation for significant low back pain in failed back surgery syndrome: design of a national, multicentre, randomized, controlled health economics trial (ESTIMET Study).

BACKGROUND: Many studies have demonstrated the efficacy of spinal cord stimulation (SCS) for chronic neuropathic radicular pain over recent decades, but despite global favourable outcomes in failed back surgery syndrome (FBSS) with leg pain, the back pain component remains poorly controlled by neurostimulation. Technological and scientific progress has led to the development of new SCS leads, comprising a multicolumn design and a greater number of contacts. The efficacy of multicolumn SCS lead configurations for the treatment of the back pain component of FBSS has recently been suggested by pilot studies. However, a randomized controlled trial must be conducted to confirm the efficacy of new generation multicolumn SCS. Évaluation médico-économique de la STImulation MEdullaire mulTi-colonnes (ESTIMET) is a multicentre, randomized study designed to compare the clinical efficacy and health economics aspects of mono- vs. multicolumn SCS lead programming in FBSS patients with radicular pain and significant back pain. MATERIALS AND METHODS: FBSS patients with a radicular pain VAS score≥50mm, associated with a significant back pain component were recruited in 14 centres in France and implanted with multicolumn SCS. Before the lead implantation procedure, they were 1:1 randomized to monocolumn SCS (group 1) or multicolumn SCS (group 2). Programming was performed using only one column for group 1 and full use of the 3 columns for group 2. Outcome assessment was performed at baseline (pre-implantation), and 1, 3, 6 and 12months post-implantation. The primary outcome measure was a reduction of the severity of low back pain (bVAS reduction≥50%) at the 6-month visit. Additional outcome measures were changes in global pain, leg pain, paraesthesia coverage mapping, functional capacities, quality of life, neuropsychological aspects, patient satisfaction and healthcare resource consumption. TRIAL STATUS: Trial recruitment started in May 2012. As of September 2013, all 14 study centres have been initiated and 112/115 patients have been enrolled. Preliminary results are expected to be published in 2015. TRIAL REGISTRATION: Clinical trial registration information-URL: www.clinicaltrials.gov. Unique identifier NCT01628237.

Infectious chest complications in haematological malignancies.

The management of infections in haematology is dictated by the patient's type of acquired or induced immune deficiency (neutropenia, deficiency in cell-mediated or antibody-mediated immunity), and findings from clinical examination, laboratory studies, or morphologic investigations. The CT scan dominates in the initial management and follow-up of these patients, since clinical features very often appear to be non-specific. The radiologist's role is to guide the clinician towards a specific diagnosis such as aspergillosis or pneumocystosis, or to point them towards a non-infectious cause: tumour localisation, hypervolaemia, bronchiolitis obliterans suggestive of GVH disease, drug toxicity, or embolism.

Modeling and evaluation of compliance to water quality regulations in bathing areas on the Daoulas catchment and estuary (France).

The microbiological quality of waters in estuaries determines their acceptability for recreational uses. Microbiological contamination often results from urban wastewater discharges or non-point source pollution (manure spreading), and can cause bathing zones to be closed. European regulations (EC/7/2006) have proposed standards (500 E. coli/100 ml) for the acceptability areas for bathing. In this study, two models were associated to simulate contamination: SWAT on a catchment and MARS 2D in the downstream estuary. After river flow calibration and validation, two scenarios were simulated in SWAT, and E. coli fluxes obtained at the main outlet of the catchment were then introduced into MARS 2D to follow E. coli concentrations in the estuary. An annual evaluation of compliance to bathing area water quality standards was then calculated, linked with daily rainfall classes. Water quality in the estuary was below the standard on 13 days, including 5 days with rainfall superior to 10 mm, due to faecal contamination from soil leaching by rain, and 5 days with rainfall ranging from 0.1 to 5 mm/day, due to the high frequency of this level of rainfall. To conclude, this study allowed us to demonstrate the efficiency of models to gain a better understanding on water quality degradation factors.