Genomics of Klebsiella pneumoniae ST16 producing NDM-1, CTX-M-15, and OXA-232

OBJECTIVES: Genomic characterization of the internationally spread sequence type (ST) 16 carbapenem-resistant Klebsiella pneumoniae. METHODS: The complete genomes of three carbapenem producing ST16 K. pneumoniae from Italian patients were analysed by single-nucleotide polymorphism-based phylogeny, core genome multilocus sequence typing, resistance, plasmid, and virulence content and compared with ten genomes of ST16 strains isolated in other countries. Plasmids carrying blaNDM-1 or blaOXA-232 carbapenemase genes were assembled and sequences were analysed. RESULTS: The internationally spread ST16 K. pneumoniae clone showed variability in terms of distribution of NDM-1 and OXA-232 type carbapenemases. In some ST16 strains, up to six plasmids can be simultaneously present in the same cell, including ColE-like plasmids carrying blaOXA-232 and IncF plasmids carrying blaNDM-1. The differences observed in plasmid, resistance, and virulence content and core genome suggested that there is not a unique, highly conserved ST16 clone, but instead different variants of this lineage circulate worldwide. CONCLUSIONS: The ST16 K. pneumoniae clone has spread worldwide and may become a high-risk clone

New onset of loss of smell or taste in household contacts of home-isolated SARS-CoV-2-positive subjects

Purpose: To estimate the prevalence of smell or taste impairment in household contacts of mildly symptomatic home-isolated SARS-CoV-2-positive patients. Methods: Cross-sectional study based on ad hoc questions. Results: Of 214 mildly symptomatic COVID-19 patients managed at home under self-isolation, 179 reported to have at least one household contact, with the total number of no study participants contacts being 296. Among 175 household contacts not tested for SARS-CoV-2 infection, 67 (38.3%) had SARS-CoV-2 compatible symptoms, 39 (22.3%) had loss of smell or taste with 7 (4.0%) having loss of smell or taste in the absence of other symptoms. The prevalence of smell or taste impairment was 1.5% in patients tested negative compared to 63.0% of those tested positive for SARS-CoV-2 (p < 0.001). Conclusion: Smell or taste impairment are quite common in not-tested household contacts of mildly symptomatic home-isolated SARS-CoV-2-positive patients. This should be taken into account when estimating the burden of loss of sense of smell and taste during COVID-19 pandemic, and further highlights the value of loss of sense of smell and taste as a marker of infection

Dopamine Increases a Value-Independent Gambling Propensity

Although the impact of dopamine on reward learning is well documented, its influence on other aspects of behavior remains the subject of much ongoing work. Dopaminergic drugs are known to increase risk-taking behavior, but the underlying mechanisms for this effect are not clear. We probed dopamine’s role by examining the effect of its precursor L-DOPA on the choices of healthy human participants in an experimental paradigm that allowed particular components of risk to be distinguished. We show that choice behavior depended on a baseline (ie, value-independent) gambling propensity, a gambling preference scaling with the amount/variance, and a value normalization factor. Boosting dopamine levels specifically increased just the value-independent baseline gambling propensity, leaving the other components unaffected. Our results indicate that the influence of dopamine on choice behavior involves a specific modulation of the attractiveness of risky options—a finding with implications for understanding a range of reward-related psychopathologies including addiction

On Vanishing Theorems For Vector Bundle Valued p-Forms And Their Applications

Let $F: [0, \infty) \to [0, \infty)$ be a strictly increasing $C^2$ function with $F(0)=0$. We unify the concepts of $F$-harmonic maps, minimal hypersurfaces, maximal spacelike hypersurfaces, and Yang-Mills Fields, and introduce $F$-Yang-Mills fields, $F$-degree, $F$-lower degree, and generalized Yang-Mills-Born-Infeld fields (with the plus sign or with the minus sign) on manifolds. When $F(t)=t, \frac 1p(2t)^{\frac p2}, \sqrt{1+2t} -1,$ and $1-\sqrt{1-2t},$ the $F$-Yang-Mills field becomes an ordinary Yang-Mills field, $p$-Yang-Mills field, a generalized Yang-Mills-Born-Infeld field with the plus sign, and a generalized Yang-Mills-Born-Infeld field with the minus sign on a manifold respectively. We also introduce the $E_{F,g}-$energy functional (resp. $F$-Yang-Mills functional) and derive the first variational formula of the $E_{F,g}-$energy functional (resp. $F$-Yang-Mills functional) with applications. In a more general frame, we use a unified method to study the stress-energy tensors that arise from calculating the rate of change of various functionals when the metric of the domain or base manifold is changed. These stress-energy tensors, linked to $F$-conservation laws yield monotonicity formulae. A "macroscopic" version of these monotonicity inequalities enables us to derive some Liouville type results and vanishing theorems for $p-$forms with values in vector bundles, and to investigate constant Dirichlet boundary value problems for 1-forms. In particular, we obtain Liouville theorems for $F-$harmonic maps (e.g. $p$-harmonic maps), and $F-$Yang-Mills fields (e.g. generalized Yang-Mills-Born-Infeld fields on manifolds). We also obtain generalized Chern type results for constant mean curvature type equations for $p-$forms on $\Bbb{R}^m$ and on manifolds $M$ with the global doubling property by a different approach. The case $p=0$ and $M=\mathbb{R}^m$ is due to Chern.Comment: 1. This is a revised version with several new sections and an appendix that will appear in Communications in Mathematical Physics. 2. A "microscopic" approach to some of these monotonicity formulae leads to celebrated blow-up techniques and regularity theory in geometric measure theory. 3. Our unique solution of the Dirichlet problems generalizes the work of Karcher and Wood on harmonic map

Human cortical organoids expose a differential function of GSK3 on cortical neurogenesis

The regulation of the proliferation and polarity of neural progenitors is crucial for the development of the brain cortex. Animal studies have implicated glycogen synthase kinase 3 (GSK3) as a pivotal regulator of both proliferation and polarity, yet the functional relevance of its signaling for the unique features of human corticogenesis remains to be elucidated. We harnessed human cortical brain organoids to probe the longitudinal impact of GSK3 inhibition through multiple developmental stages. Chronic GSK3 inhibition increased the proliferation of neural progenitors and caused massive derangement of cortical tissue architecture. Single-cell transcriptome profiling revealed a direct impact on early neurogenesis and uncovered a selective role of GSK3 in the regulation of glutamatergic lineages and outer radial glia output. Our dissection of the GSK3-dependent transcriptional network in human corticogenesis underscores the robustness of the programs determining neuronal identity independent of tissue architecture

Human resources for health at the district level in Indonesia: the smoke and mirrors of decentralization

<p>Abstract</p> <p>Background</p> <p>In 2001 Indonesia embarked on a rapid decentralization of government finances and functions to district governments. One of the results is that government has less information about its most valuable resource, the people who provide the services. The objective of the work reported here is to determine the stock of human resources for health in 15 districts, their service status and primary place of work. It also assesses the effect of decentralization on management of human resources and the implications for the future.</p> <p>Methods</p> <p>We enumerated all health care providers (doctors, nurses and midwives), including information on their employment status and primary place of work, in each of 15 districts in Java. Data were collected by three teams, one for each province.</p> <p>Results</p> <p>Provider density (number of doctors, nurses and midwives/1000 population) was low by international standards – 11 out of 15 districts had provider densities less than 1.0. Approximately half of all three professional groups were permanent public servants. Contractual employment was also important for both nurses and midwives. The private sector as the primary source of employment is most important for doctors (37% overall) and increasingly so for midwives (10%). For those employed in the public sector, two-thirds of doctors and nurses work in health centres, while most midwives are located at village-level health facilities.</p> <p>Conclusion</p> <p>In the health system established after Independence, the facilities established were staffed through a period of obligatory service for all new graduates in medicine, nursing and midwifery. The last elements of that staffing system ended in 2007 and the government has not been able to replace it. The private sector is expanding and, despite the fact that it will be of increasing importance in the coming decades, government information about providers in private practice is decreasing. Despite the promise of decentralization to increase sectoral "decision space" at the district level, the central government now has control over essentially all public sector health staff at the district level, marking a return to the situation of 20 years ago. At the same time, Indonesia has changed dramatically. The challenge now is to envision a new health system that takes account of these changes. Envisioning the new system is a crucial first step for development of a human resources policy which, in turn, will require more information about health care providers, public and private, and increased capacity for human resource planning.</p

Motor coordination, working memory, and academic achievement in a normative adolescent sample: Testing a mediation model

The aim of the present study was to examine whether the relationship between motor coordination and academic achievement is mediated by working memory (WM) in a normative adolescent sample. Participants included 93 adolescents aged 12–16. The Movement Assessment Battery for Children-2 provided three indicators of motor coordination (Manual Dexterity, Aiming and Catching, and Balance), the WM Index of the Wechsler Intelligence Scale for Children-IV and the N-back paradigm provided two indicators of WM, and the Wechsler Individual Achievement Test-II provided three indicators of academic achievement (Word Reading, Spelling, and Numerical Operations). Structural equation modeling, controlling for verbal comprehension, attention deficit hyperactivity disorder symptoms, and socioeconomic status, suggested that the association between motor coordination and academic achievement may be best understood in terms of a mechanism whereby motor coordination (specifically, Aiming and Catching skills) has an indirect impact on academic outcomes via WM. These findings have important implications for the assessment and treatment of motor coordination and learning difficulties as well as in increasing the understanding of the possible neural mechanisms underpinning the relationship between these areas