A Conceptual Discussion About the Basic Reproduction Number of Severe Acute Respiratory Syndrome Coronavirus 2 in Healthcare Settings.

To date, no specific estimate of R0 for SARS-CoV-2 is available for healthcare settings. Using interindividual contact data, we highlight that R0 estimates from the community cannot translate directly to healthcare settings, with pre-pandemic R0 values ranging 1.3-7.7 in 3 illustrative healthcare institutions. This has implications for nosocomial COVID-19 control.

Investigation of the Relationships Between Clinical and Environmental Isolates of Aspergillus fumigatus by Multiple-locus Variable Number Tandem Repeat Analysis During Major Demolition Work in a French Hospital.

Background: Genotyping is needed to explore the link between clinical cases from colonization of invasive aspergillosis (IA) and major building construction. Attempts to correlate Aspergillus fumigatus strains from clinical infection or colonization with those found in the environment remain controversial due to the lack of a large prospective study. Our aim in this study was to compare the genetic diversity of clinical and environmental A. fumigatus isolates during a demolition period. Methods: Fungal contamination was monitored daily for 11 months in 2015. Environmental surveillance was undertaken indoors and outdoors at 8 locations with automatic agar samplers. IA infection cases were investigated according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria. Isolates were identified by amplification and sequencing of the ß- tubulin gene. They were genotyped by multiple-locus variable number tandem repeat analysis (MLVA). The phylogenetic relationships between isolates were assessed by generating a minimum spanning tree. Results: Based on 3885 samples, 394 A. fumigatus isolates (383 environmental and 11 clinical) were identified and genotyped using MLVA. Clinical isolates were collected from patients diagnosed as having probable IA (n = 2), possible IA (n = 1), or bronchial colonization (n = 6). MLVA generated 234 genotypes. Seven clinical isolates shared genotypes identical to environmental isolates. Conclusions: Among the diversity of genotypes described, similar genotypes were found in clinical and environmental isolates, indicating that A. fumigatus infection and colonization may originate from hospital environments.

Lost in Transit: Long-Distance Trafficking and Phloem Unloading of Protein Signals in Arabidopsis Homografts.

In addition to moving sugars and nutrients, the phloem transports many macromolecules. While grafting and aphid stylectomy experiments have identified many macromolecules that move in the phloem, the functional significance of phloem transport of these remains unclear. To gain insight into protein trafficking, we micrografted Arabidopsis thaliana scions expressing GFP-tagged chloroplast transit peptides under the 35S promoter onto nontransgenic rootstocks. We found that plastids in the root tip became fluorescent 10 d after grafting. We obtained identical results with the companion cell-specific promoter SUC2 and with signals that target proteins to peroxisomes, actin, and the nucleus. We were unable to detect the respective mRNAs in the rootstock, indicating extensive movement of proteins in the phloem. Outward movement from the root protophloem was restricted to the pericycle-endodermis boundary, identifying plasmodesmata at this interface as control points in the exchange of macromolecules between stele and cortex. Intriguingly, signals directing proteins to the endoplasmic reticulum and Golgi apparatus from membrane-bound ribosomes were not translocated to the root. It appears that many organelle-targeting sequences are insufficient to prevent the loss of their proteins into the translocation stream. Thus, nonspecific loss of proteins from companion cells to sieve elements may explain the plethora of macromolecules identified in phloem sap.

Estimation of Extra Length of Stay Attributable to Hospital-Acquired Infections in Adult ICUs Using a Time-Dependent Multistate Model.

OBJECTIVES: The objective of the study was to estimate the length of stay of patients with hospital-acquired infections hospitalized in ICUs using a multistate model. DESIGN: Active prospective surveillance of hospital-acquired infection from January 1, 1995, to December 31, 2012. SETTING: Twelve ICUs at the University of Lyon hospital (France). PATIENTS: Adult patients age greater than or equal to 18 years old and hospitalized greater than or equal to 2 days were included in the surveillance. All hospital-acquired infections (pneumonia, bacteremia, and urinary tract infection) occurring during ICU stay were collected. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The competitive risks of in-hospital death, transfer, or discharge were considered in estimating the change in length of stay due to infection(s), using a multistate model, time of infection onset. Thirty-three thousand four-hundred forty-nine patients were involved, with an overall hospital-acquired infection attack rate of 15.5% (n = 5,176). Mean length of stay was 27.4 (± 18.3) days in patients with hospital-acquired infection and 7.3 (± 7.6) days in patients without hospital-acquired infection. A multistate model-estimated mean found an increase in length of stay by 5.0 days (95% CI, 4.6-5.4 d). The extra length of stay increased with the number of infected site and was higher for patients discharged alive from ICU. No increased length of stay was found for patients presenting late-onset hospital-acquired infection, more than the 25th day after admission. CONCLUSIONS: An increase length of stay of 5 days attributable to hospital-acquired infection in the ICU was estimated using a multistate model in a prospective surveillance study in France. The dose-response relationship between the number of hospitalacquired infection and length of stay and the impact of early-stage hospital-acquired infection may strengthen attention for clinicians to focus interventions on early preventions of hospital-acquired infection in ICU.

ITPA Activity in Adults and Children Treated With or Without Azathioprine: Relationship Between TPMT Activity, Thiopurine Metabolites, and Co-medications.

BACKGROUND: The implication of inosine triphosphate pyrophosphatase (ITPA) on thiopurine drug response variability has been investigated but little data are available on its role on thiopurine metabolites. The ability of ITPA to modify the thiopurine metabolite levels is currently used to optimize azathioprine (AZA) therapy in relation to thiopurine S-methyltransferase (TPMT) activity, the aim of this study is to investigate ITPA phenotype in a large population and to evaluate the relation between ITPA and TPMT activities and thiopurine metabolites. METHODS: ITPA activity was determined in 183 adults and 138 children with or without AZA therapy. 6-thioguanine nucleotides (6-TGN), 6-methylmercaptopurine nucleotides (6-MeMPN) levels, and ITPA as well as TPMT activities were measured in red blood cells. Using the Gaussian mixture model, distribution of ITPA activity was evaluated. Intraindividual variability and influence of age, sex, AZA treatment and associated co-medications on ITPA activity were also assessed. RESULTS: This retrospective study shows a quadrimodal distribution in ITPA activity. No influence of age, sex, AZA therapy, and co-medications was found. In adults, ITPA activity was not significantly associated with 6-TGN or 6-MeMPN concentrations, whereas a weak negative correlation was observed with 6-MeMPN levels in pediatric populations (rs = -0.261; P = 0.024). A weak positive correlation was observed between ITPA and TPMT activities in children (rs = 0.289; P = 0.001). CONCLUSIONS: ITPA activity was poorly influenced by nongenetic parameters and has no influence on 6-TGN and 6-MeMPN concentrations in adults and only a weak correlation with 6-MeMPN and TPMT activity in children. These results demonstrate that ITPA is not a rate-limiting enzyme in the formation of 6-TGN but suggest that a decrease in ITPA activity in children may be a risk factor for accumulation of 6-MeMPN in cells.

Comparison of four different fuller's earth formulations in skin decontamination.

Industrial accidents, wars and terrorist threats are potential sources of skin contamination by highly toxic chemical warfare agents and manufacturing compounds. We have compared the time-dependent adsorption capacity and decontamination efficiency of fuller's earth (FE) for four different formulations for the molecular tracer, 4-cyanophenol (4-CP), in vitro and ex vivo using water decontamination as standard. The adsorption capacity of FE was assessed in vitro for 4-CP aqueous solutions whereas decontamination efficiency was investigated ex vivo by tracking porcine skin 4-CP content using attenuated total reflectance Fourier transform infrared spectroscopy. Decontamination was performed on short time, exposed porcine skin to 4-CP by application of FE: (1) as free powder; (2) loaded on adhesive tape; (3) on powdered glove; or (4) in suspension. Removal rate of 4-CP from aqueous solutions correlates with the amount of FE and its contact time. Decontamination efficiency estimated by the percentage of 4-CP recovery from contaminated porcine skin, achieved 54% with water, ranged between ~60 and 70% with dry FE and reached ~90% with FE suspension. Successful decontamination of the FE suspension, enabling a dramatic reduction of skin contamination after a brief exposure scenario, appears to be rapid, reliable and should be formulated in a new device ready to use for self-application.

Relearn Faster and Retain Longer.

Both repeated practice and sleep improve long-term retention of information. The assumed common mechanism underlying these effects is memory reactivation, either on-line and effortful or off-line and effortless. In the study reported here, we investigated whether sleep-dependent memory consolidation could help to save practice time during relearning. During two sessions occurring 12 hr apart, 40 participants practiced foreign vocabulary until they reached a perfect level of performance. Half of them learned in the morning and relearned in the evening of a single day. The other half learned in the evening of one day, slept, and then relearned in the morning of the next day. Their retention was assessed 1 week later and 6 months later. We found that interleaving sleep between learning sessions not only reduced the amount of practice needed by half but also ensured much better long-term retention. Sleeping after learning is definitely a good strategy, but sleeping between two learning sessions is a better strategy.

High bicarbonate levels in narcoleptic children.

The objective of this study was to evaluate the levels of plasma bicarbonate levels in narcoleptic children. Clinical, electrophysiological data and bicarbonate levels were evaluated retrospectively in children seen in our paediatric national reference centre for hypersomnia. The cohort included 23 control subjects (11.5 ± 4 years, 43% boys) and 51 patients presenting de-novo narcolepsy (N) (12.7 ± 3.7 years, 47% boys). In narcoleptic children, cataplexy was present in 78% and DQB1*0602 was positive in 96%. The control children were less obese (2 versus 47%, P = 0.001). Compared with control subjects, narcoleptic children had higher bicarbonate levels (P = 0.02) as well as higher PCO2 (P < 0.01) and lower venous pH gas (P < 0.01). Bicarbonate levels higher than 27 mmol L(-1) were found in 41.2% of the narcoleptic children and 4.2% of the controls (P = 0.001). Bicarbonate levels were correlated with the Adapted Epworth Sleepiness Scale (P = 0.01). Narcoleptic patients without obesity often had bicarbonate levels higher than 27 mmol L (-1) (55 versus 25%, P = 0.025). No differences were found between children with and without cataplexy. In conclusion, narcoleptic patients had higher bicarbonate plasma levels compared to control children. This result could be a marker of hypoventilation in this pathology, provoking an increase in PCO2 and therefore a respiratory acidosis, compensated by an increase in plasma bicarbonates. This simple screening tool could be useful for prioritizing children for sleep laboratory evaluation in practice.

Computational identification of potential transcriptional regulators of TGF-ß1 in human atherosclerotic arteries.

TGF-ß is protective in atherosclerosis but deleterious in metastatic cancers. Our aim was to determine whether TGF-ß transcriptional regulation is tissue-specific in early atherosclerosis. The computational methods included 5 steps: (i) from microarray data of human atherosclerotic carotid tissue, to identify the 10 best co-expressed genes with TGFB1 (TGFB1 gene cluster), (ii) to choose the 11 proximal promoters, (iii) to predict the TFBS shared by the promoters, (iv) to identify the common TFs co-expressed with the TGFB1 gene cluster, and (v) to compare the common TFs in the early lesions to those identified in advanced atherosclerotic lesions and in various cancers. Our results show that EGR1, SP1 and KLF6 could be responsible for TGFB1 basal expression, KLF6 appearing specific to atherosclerotic lesions. Among the TFs co-expressed with the gene cluster, transcriptional activators (SLC2A4RG, MAZ) and repressors (ZBTB7A, PATZ1, ZNF263) could be involved in the fine-tuning of TGFB1 expression in atherosclerosis.

Early Periimplant Tissue Healing on 1-Piece Implants With a Concave Transmucosal Design: A Histomorphometric Study in Dogs.

INTRODUCTION: The purpose of our study was to investigate the early healing phase of marginal bone and soft tissues around unloaded 1-piece implants with a concave transmucosal design, in a dog model. METHODS: Twenty-four 1-piece implants with a concave transmucosal neck were inserted 1 mm subcrestally in the mandibular ridge of 8 beagle dogs. Four animals were sacrificed after 3 and 12 weeks of healing. Histomorphometric analysis was performed to measure the height of the periimplant tissues. RESULTS AND DISCUSSION: The overall height of the periimplant mucosa was, respectively, 2.67 and 2.52 mm, after 3 and 12 weeks. In the connective tissue, a soft tissue O-ring seal was observed in the healing area provided by the transmucosal concavity, after 12 weeks. The location of the first bone-to-implant contact facing the implant shoulder was 0.00 and +0.18 mm, respectively, after 3 and 12 weeks of healing. Some bone apposition occurred on the implant shoulder during the healing. CONCLUSION: Within the limits of the present study, a concave transmucosal design in 1-piece implants was associated with a short vertical value of biological width and promoted a mechanical interlocking of the implant body at the connective tissue and marginal bone levels.

Treatment for behavioral insomnia in young children with neurotypical development under 6 years of age: A systematic review.

This literature review examines all treatments for behavioral insomnia in children under 6 years of age to determine which treatments have empirically demonstrated efficacy. Following PRISMA guidelines, three databases were investigated (Pubmed, Cochrane and Psychinfo) to select randomized controlled trials (RCTs) which assess treatments for behavioral insomnia in children under 6 years of age, all with neurotypical development. A total of 908 articles met the search criteria. 21 articles were selected and analyzed in their entirety for a total of 2363 children (ranging from 2 months to 6 years of age). Based on these studies, treatment of behavioral insomnia in young children under 6 years of age is primarily based on behavioral therapy. There is no evidence that pharmacological treatments are effective in the long term for neurotypical children. This review highlights the lack of RCTs in this field: new RCTs should be carried out among young children to refine and optimize the therapeutic approach and to address the risk of therapeutic abuse through the use of non-scientifically validated methods.

Early adverse changes in liver microvascular circulation during experimental septic shock are not linked to an absolute nitric oxide deficit.

Nitric oxide (NO) is believed to play a key role in adverse microvascular changes during sepsis. A deficit in NO has been evoked as a potential mechanism of microcirculatory deterioration in the early phase of septic shock. The aim of this study was to evaluate simultaneously and continuously both hepatic microcirculation and local NO production during early experimental sepsis. Wistar male rats were divided into two groups: a sepsis group undergoing cecal ligation and puncture (CLP) peritonitis and a control group undergoing sham surgery. Hepatic microcirculation was continuously monitored using a laser Doppler probe and local nitric oxide (NO) production by means of a specific electrode. Constitutive and inducible NO synthase production was assessed 2h after surgery, at onset of shock, and at 2 and 3h after shock. In control animals, hepatic microcirculatory perfusion and NO production remained stable throughout the experiment. In septic animals, whereas a fall in microcirculatory perfusion was noted as early as 2h after CLP, NO concentration remained stable and further increased after the onset of shock. At this time, inducible NO synthase was the only isoform significantly elevated. In this non-resuscitated experimental model of sepsis, an absolute liver deficit of NO could not explain the early adverse changes in the local microvascular system.

Influenza transmissibility among patients and health-care professionals in a geriatric short-stay unit using individual contact data.

Detailed information are lacking on influenza transmissibility in hospital although clusters are regularly reported. In this pilot study, our goal was to estimate the transmission rate of H3N2 2012-influenza, among patients and health care professionals in a short-term Acute Care for the Elderly Unit by using a stochastic approach and a simple susceptible-exposed-infectious-removed model. Transmission parameters were derived from documented individual contact data collected by Radio Frequency IDentification technology at the epidemic peak. From our model, nurses appeared to transmit infection to a patient more frequently with a transmission rate of 1.04 per day on average compared to 0.38 from medical doctors. This transmission rate was 0.34 between nurses. These results, even obtained in this specific context, might give a relevant insight of the influenza dynamics in hospitals and will help to improve and to target control measures for preventing nosocomial transmission of influenza. The investigation of nosocomial transmission of SARS-COV-2 might gain from similar approaches.

Enriched PUFA environment of Leishmania infantum promastigotes promotes the accumulation of lipid mediators and favors parasite infectivity towards J774 murine macrophages.

Leishmania parasites are the causative agents of visceral or cutaneous leishmaniasis in humans and of canine leishmaniosis. The macrophage is the predilected host cell of Leishmania in which the promastigote stage is transformed into amastigote. We previously showed changes in the fatty acid composition (FA) of lipids in two strains of Leishmania donovani upon differentiation of promastigote to amastigote, including increased proportions of arachidonic acid (AA) and to a less extent of docosahexaenoic acid (DHA). Here, we carried out supplementation with AA or DHA on two Leishmania infantum strains, a visceral (MON-1) and a cutaneous (MON-24), to evaluate the role of these FA in parasite/macrophage interactions. The proportions of AA or DHA in total lipids were significantly increased in promastigotes cultured in AA- or DHA-supplemented media compared to controls. The content of FA-derived oxygenated metabolites was enhanced in supplemented strains, generating especially epoxyeicosatrienoic acids (11,12- and 14,15-EET) and hydroxyeicosatetraenoic acids (5- and 8- HETE) from AA, and hydroxydocosahexaenoic acids (14- and 17-HDoHE) from DHA. For both MON-1 and MON-24, AA-supplemented promastigotes showed higher infectivity towards J774 macrophages as evidenced by higher intracellular amastigote numbers. Higher infectivity was observed after DHA supplementation for MON-24 but not MON-1 strain. ROS production by macrophages increased upon parasite infection, but only minor change was observed between control and supplemented parasites. We propose that under high AA or DHA environment that is associated with AA or DHA enrichment of promastigote lipids, FA derivatives can accumulate in the parasite, thereby modulating parasite infectivity towards host macrophages.

Geometric and harmonic study of the aging of the fourth rib.

One of the current reference methods, namely the Iscan method for estimating age at death, consists in the subjective observation of the sternal end of the fourth rib. In this study, we looked to identify the morphometric characteristics of the sternal end of the fourth rib that were most affected by aging by measuring them in an objective way. For this purpose, we collected measurements from the fourth rib tip of 414 French males and used mathematical algorithms derived from pattern recognition and signal processing to identify variables that reflect both geometric characteristics and serration patterns of the ribs. Completed analysis was carried out on the 284 ribs for which all the variables could be collected. We showed that the three least collinear variables that best explain age objectively are the postero-superior pit depth, the fine serrations of the ovoid (delineating the pit shape), and its posterior flaring. This work provides a useful basis for subsequent studies on aging and age prediction.

Analytical investigation of salivary calculi, by mid-infrared spectroscopy.

Sialolithiasis is common in salivary glands, especially in the submandibular and parotid ducts. X-Ray diffractometry was the principal technique used for their analysis, sometimes associated with scanning electron microscopy. Hydroxyapatite was the most frequently described constituent, in association with whitlockite and other calcium phosphates as brushite or octocalcium phosphate. Proteic matter was detected, as mucoproteins, albumin, nucleoproteins or as degenerative bacterial matter. This study presents the identification of constituents by mid-infrared spectrometry of 74 sialoliths. Their successive layers are analyzed from their crust to the nucleus, using absorbance measurements. Spectra are compared with reference mixtures of two or more constituents. Approximately 99% of sialoliths are constituted of calcium phosphates, under carbonated forms. More than three-quarters contain proteins, in which mucins represent the majority and albumin is found in 10% of all the specimens. Only 7% calculi are an association of two constituents, 66% are made of three and 27% have four or more components. For the 74 studied sialoliths, no specimen contains hydroxyapatite; but they are composed of carbonate apatites with irregular microcrystallized forms, even if proteins are present. Some of them have a pure protein nucleus, surrounded by carbonate apatite layers; the other stones are made of internal layers of apatites and covered with a dense and varnished crust of proteins.

Development and Cross-National Validation of a French Version of the Jefferson Scale of Empathy for Students.

Empathy is a multifaceted personal ability combining emotional and cognitive features modulated by cultural specificities. It is widely recognized as a key clinical competence that should be valued during professional training. The Jefferson Scale of Empathy for medical students (JSE-S) has been developed for this purpose and validated in several languages, but not in French. The aims of this study were to gather validity evidence for a newly developed version of the JSE-S and compare it between two French-speaking contexts. In total, 1,433 undergraduate medical students from the universities of Lyon (UL), France and Geneva (UG), Switzerland participated in the study completing the JSE-S in French. Total and partial scores of the three subscales ("perspective taking," "compassionate care" and "walking in patient's shoes") were calculated for each site. Construct validity of the JSE-S was analyzed considering three sources of evidence: content, internal structure and relations to other variables. A first-order Confirmatory Factor Analysis using structural equation modeling examined the three latent variables of the JSE-S subscales. Cronbach's α coefficients were 0.75 (UG) and 0.81 (UL). The items' discrimination power ranged between 0.29 and 1.60 (median effect size of 1.24). The overall correlations between items and total or partial scores derived from the latent JSE-S subscales were consistently similar in both study sites. Findings of this study confirm the latent structure of the JSE-S in French and its cross-national reproducibility. The comparable underlying structure of the questionnaire tested in two distinct French-speaking contexts endorses the generalizability of its measure.

Baseline clinical features of COVID-19 patients, delay of hospital admission and clinical outcome: A complex relationship.

INTRODUCTION: Delay between symptom onset and access to care is essential to prevent clinical worsening for different infectious diseases. For COVID-19, this delay might be associated with the clinical prognosis, but also with the different characteristics of patients. The objective was to describe characteristics and symptoms of community-acquired (CA) COVID-19 patients at hospital admission according to the delay between symptom onset and hospital admission, and to identify determinants associated with delay of admission. METHODS: The present work was based on prospective NOSO-COR cohort data, and restricted to patients with laboratory confirmed CA SARS-CoV-2 infection admitted to Lyon hospitals between February 8 and June 30, 2020. Long delay of hospital admission was defined as ≥6 days between symptom onset and hospital admission. Determinants of the delay between symptom onset and hospital admission were identified by univariate and multiple logistic regression analysis. RESULTS: Data from 827 patients were analysed. Patients with a long delay between symptom onset and hospital admission were younger (p<0.01), had higher body mass index (p<0.01), and were more frequently admitted to intensive care unit (p<0.01). Their plasma levels of C-reactive protein were also significantly higher (p<0.01). The crude in-hospital fatality rate was lower in this group (13.3% versus 27.6%), p<0.01. Multiple analysis with correction for multiple testing showed that age ≥75 years was associated with a short delay between symptom onset and hospital admission (≤5 days) (aOR: 0.47 95% CI (0.34-0.66)) and CRP>100 mg/L at admission was associated with a long delay (aOR: 1.84 95% CI (1.32-2.55)). DISCUSSION: Delay between symptom onset and hospital admission is a major issue regarding prognosis of COVID-19 but can be related to multiple factors such as individual characteristics, organization of care and severe pathogenic processes. Age seems to play a key role in the delay of access to care and the disease prognosis.

Interpretation of drug concentrations in an alternative matrix: the case of meprobamate in vitreous humor.

The use of vitreous humor (VH) as an alternative matrix to blood in the field of forensic toxicology has been described for numerous drugs. Interpretation of drug concentrations measured in VH, as in other matrices, requires statistical analysis of a data set obtained on a significant series. In the present study, two diagnostic tests interpreting postmortem VH concentrations of meprobamate in 117 sets of autopsy data are reported. (1) A VH meprobamate concentration threshold of 28 mg/l was statistically equivalent to that of blood meprobamate concentration threshold of 50 mg/l distinguishing overdose from therapeutic use in blood. The intrinsic qualities of the test were good, with sensitivity of 0.95 and absolute specificity of 1. (2) A novel interpretation tool is proposed, allowing blood concentration range to be evaluated, with a known probability, from VH concentration.