Bacterial ‘Cell’ Phones: Do cell phones carry potential pathogens?

Cell phones are important companions for professionals especially health care workers (HCWs) for better communication in hospital. The present study compared the nature of the growth of potentially pathogenic bacterial flora on cell phones in hospital and community. 75% cell phones from both the categories grew at least one potentially pathogenic organism. Cell phones from HCWs grew significantly more potential pathogens like MRSA (20%), Acinetobacter species (5%), Pseudomonas species (2.5%) as compared to the non HCWs. 97.5% HCWs use their cell phone in the hospital, 57.5% never cleaned their cell phone and 20% admitted that they did not wash their hands before or after attending patients, although majority (77.5%) knows that cell phones can have harmful colonization and act as vector for nosocomial infections. It is recommended, therefore, that cell phones in the hospital should be regularly decontaminated. Moreover, utmost emphasis needs to be paid to hand washing practices among HCWs

De novo design of a transmembrane Zn²⁺-transporting four-helix bundle.

The design of functional membrane proteins from first principles represents a grand challenge in chemistry and structural biology. Here, we report the design of a membrane-spanning, four-helical bundle that transports first-row transition metal ions Zn(2+) and Co(2+), but not Ca(2+), across membranes. The conduction path was designed to contain two di-metal binding sites that bind with negative cooperativity. X-ray crystallography and solid-state and solution nuclear magnetic resonance indicate that the overall helical bundle is formed from two tightly interacting pairs of helices, which form individual domains that interact weakly along a more dynamic interface. Vesicle flux experiments show that as Zn(2+) ions diffuse down their concentration gradients, protons are antiported. These experiments illustrate the feasibility of designing membrane proteins with predefined structural and dynamic properties

Fracture in Mode I using a Conserved Phase-Field Model

We present a continuum phase-field model of crack propagation. It includes a phase-field that is proportional to the mass density and a displacement field that is governed by linear elastic theory. Generic macroscopic crack growth laws emerge naturally from this model. In contrast to classical continuum fracture mechanics simulations, our model avoids numerical front tracking. The added phase-field smoothes the sharp interface, enabling us to use equations of motion for the material (grounded in basic physical principles) rather than for the interface (which often are deduced from complicated theories or empirical observations). The interface dynamics thus emerges naturally. In this paper, we look at stationary solutions of the model, mode I fracture, and also discuss numerical issues. We find that the Griffith's threshold underestimates the critical value at which our system fractures due to long wavelength modes excited by the fracture process.Comment: 10 pages, 5 figures (eps). Added 2 figures and some text. Removed one section (and a figure). To be published in PR

Diagnosing Mitochondrial Disorders Remains Challenging in the Omics Era

Objective: We hypothesized that novel investigative pathways are needed to decrease diagnostic odysseys in pediatric mitochondrial disease and sought to determine the utility of clinical exome sequencing in a large cohort with suspected mitochondrial disease and to explore whether any of the traditional indicators of mitochondrial disease predict a confirmed genetic diagnosis. Methods: We investigated a cohort of 85 pediatric patients using clinical exome sequencing and compared the results with the outcome of traditional diagnostic tests, including biochemical testing of routine parameters (lactate, alanine, and proline), neuroimaging, and muscle biopsy with histology and respiratory chain enzyme activity studies. Results: We established a genetic diagnosis in 36.5% of the cohort and report 20 novel disease-causing variants (1 mitochondrial DNA). Counterintuitively, routine biochemical markers were more predictive of mitochondrial disease than more invasive and elaborate muscle studies. Conclusions: We propose using biochemical markers to support the clinical suspicion of mitochondrial disease and then apply first-line clinical exome sequencing to identify a definite diagnosis. Muscle biopsy studies should only be used in clinically urgent situations or to confirm an inconclusive genetic result. Classification of Evidence: This is a Class II diagnostic accuracy study showing that the combination of CSF and plasma biochemical tests plus neuroimaging could predict the presence or absence of exome sequencing confirmed mitochondrial disorders

Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front.

Antitumoral immunity requires organized, spatially nuanced interactions between components of the immune tumor microenvironment (iTME). Understanding this coordinated behavior in effective versus ineffective tumor control will advance immunotherapies. We re-engineered co-detection by indexing (CODEX) for paraffin-embedded tissue microarrays, enabling simultaneous profiling of 140 tissue regions from 35 advanced-stage colorectal cancer (CRC) patients with 56 protein markers. We identified nine conserved, distinct cellular neighborhoods (CNs)-a collection of components characteristic of the CRC iTME. Enrichment of PD-1+CD4+ T cells only within a granulocyte CN positively correlated with survival in a high-risk patient subset. Coupling of tumor and immune CNs, fragmentation of T cell and macrophage CNs, and disruption of inter-CN communication was associated with inferior outcomes. This study provides a framework for interrogating how complex biological processes, such as antitumoral immunity, occur through concerted actions of cells and spatial domains

Cross-sectional study of a UK cohort of neonatal vein of Galen malformation

Objective: Describe the course and outcomes in a UK national cohort of neonates with vein of Galen malformation (VGM) identified before 28 days of life. // Methods: Neonates with angiographically confirmed vein of Galen malformation presenting to one of the two UK treatment centres (2006‐2016) were included; those surviving were invited to participate in neurocognitive assessment. Results in each domain were dichotomised into “good” and “poor” categories. Cross‐sectional and angiographic brain imaging studies were systematically interrogated. Logistic regression was used to explore potential outcome predictors. // Results: Of 85 children with neonatal vein of Galen malformation, 51 had survived. Thirty‐four participated in neurocognitive assessment. Outcomes were approximately evenly split between “good” and “poor” categories across all domains, namely neurological status, general cognition, neuromotor skills, adaptive behaviour, and emotional and behavioural development. Important predictors of poor cognitive outcome were initial Bicetre score </=12 and presence of brain injury, specifically white matter injury, on initial imaging; in multivariable analysis only Bicetre score </=12 remained significant. // Interpretation: Despite modern supportive and endovascular treatment, over a third of unselected newborns with vein of Galen malformation did not survive. Outcome was good in around half of survivors. The importance of white matter injury suggests that abnormalities of venous, as well as arterial, circulation are important in pathophysiology of brain injury

Diagnostic algorithm for children presenting with epilepsia partialis continua

Objective: To characterize a cohort of children with epilepsia partialis continua (EPC) and develop a diagnostic algorithm incorporating key differential diagnoses. / Methods: Children presenting with EPC to a tertiary pediatric neurology center between 2002 and 2019 were characterized. / Results: Fifty‐four children fulfilled EPC criteria. Median age at onset was 7 years (range 0.6‐15), with median follow‐up of 4.3 years (range 0.2‐16). The diagnosis was Rasmussen encephalitis (RE) in 30 of 54 (56%), a mitochondrial disorder in 12 of 54 (22.2%), and magnetic resonance imaging (MRI) lesion‐positive focal epilepsy in 6 of 54 (11.1%). No diagnosis was made in 5 of 54 (9%). Children with mitochondrial disorders developed EPC earlier; each additional year at presentation reduced the odds of a mitochondrial diagnosis by 26% (P = .02). Preceding developmental concerns (odds ratio [OR] 22, P < .001), no seizures prior to EPC (OR 22, P < .001), bilateral slowing on electroencephalogram (EEG) (OR 26, P < .001), and increased cerebrospinal fluid (CSF) protein level (OR 16) predicted a mitochondrial disorder. Asymmetry or hemiatrophy was evident on MRI at presentation with EPC in 18 of 30 (60%) children with RE, and in the remainder at a median of 6 months (range 3‐15) after EPC onset. The first diagnostic test is brain MRI. Hemiatrophy may permit a diagnosis of RE with unilateral clinical and EEG findings. For children in whom a diagnosis of RE cannot be made on first scan but the clinical and radiological presentation resembles RE, repeat imaging every 6 months is recommended to detect progressive unicortical hemiatrophy, and brain biopsy should be considered. Evidence of intrathecal inflammation (oligoclonal bands and raised neopterin) can be supportive. In children with bihemispheric EPC, rapid polymerase gamma testing is recommended and if negative, sequencing mtDNA and whole‐exome sequencing on blood‐derived DNA should be performed. / Significance: Children presenting with EPC due to a mitochondrial disorder show clinical features distinguishing them from RE and structural epilepsies. A diagnostic algorithm for children with EPC will allow targeted investigation and timely diagnosis

Atomistic simulations of dislocation mobility in Al, Ni and Al/Mg alloys

Dislocation velocities and mobilities are studied by Molecular Dynamics simulations for edge and screw dislocations in pure aluminum and nickel, and edge dislocations in Al-2.5%Mg and Al-5.0%Mg random substitutional alloys using EAM potentials. In the pure materials, the velocities of all dislocations are close to linear with the ratio of (applied stress)/(temperature) at low velocities, consistent with phonon drag models and quantitative agreement with experiment is obtained for the mobility in Al. At higher velocities, different behavior is observed. The edge dislocation velocity remains dependent solely on (applied stress)/(temperature) up to approximately 1.0 MPa/K, and approaches a plateau velocity that is lower than the smallest "forbidden" speed predicted by continuum models. In contrast, above a velocity around half of the smallest continuum wave speed, the screw dislocation damping has a contribution dependent solely on stress with a functional form close to that predicted by a radiation damping model of Eshelby. At the highest applied stresses, there are several regimes of nearly constant (transonic or supersonic) velocity separated by velocity gaps in the vicinity of forbidden velocities; various modes of dislocation disintegration and destabilization were also encountered in this regime. In the alloy systems, there is a temperature- and concentration-dependent pinning regime where the velocity drops sharply below the pure metal velocity. Above the pinning regime but at moderate stresses, the velocity is again linear in (applied stress)/(temperature) but with a lower mobility than in the pure metal.Comment: PDF, 30 pages including figures, submitted to Modelling Simul. Mater. Sci. En

Transformative or Functional Justice? Examining the Role of Health Care Institutions in Responding to Violence Against Women in India

With the growing salience of ideas and reforms concerning women’s human rights and gender equality, violence against women (VAW) has received heightened policy attention. Recent global calls for ending VAW identify health care systems as having a crucial role in a multisector response to tackle this social injustice. Scholars emphasize the transformative potential of such response in its ability to not only address the varied health consequences but also prevent future recurrence by enabling wider access to support and justice. This wider consensus on the role of health systems, however, demands stronger empirical basis. This article reports findings from an exploratory research developed around the core question: What are the perceived strengths and challenges confronting health systems in offering a comprehensive response to VAW in India? Drawing on site visits, observations, and interviews with front-line staff and program managers of an integrated intervention to tackle violence in Kerala and nongovernment organisation staff in Delhi and Mumbai, the article presents its historical context and key barriers to effective implementation. While promising in terms of outreach and incremental changes in attitudes, barriers include deficits in infrastructure and institutional practices that reinforce inequities in gender–power relations, hostile attitudes, and limited capacities of health workforce to tackle the complex and diverse needs of women experiencing abuse. Locating these experiences in relation to other models rooted in feminist approach, I argue how conventional intervention models of provisioning fail to challenge institutional contexts and structural inequalities that underpin violence and compound vulnerabilities experienced by women, thereby serving a functional response. Health systems are social institutions embedded in prevailing gender norms and power relations that must be tackled alongside addressing imminent needs of women victims of abuse. To this end, feminist approaches to counselling and relational perspectives to social justice can strengthen responsiveness (and transformative potential) of integrated sector-wide interventions

Landscape of coordinated immune responses to H1N1 challenge in humans

Influenza is a significant cause of morbidity and mortality worldwide. Here we show changes in the abundance and activation states of more than 50 immune cell subsets in 35 individuals over 11 time points during human A/California/2009 (H1N1) virus challenge monitored using mass cytometry along with other clinical assessments. Peak change in monocyte, B cell, and T cell subset frequencies coincided with peak virus shedding, followed by marked activation of T and NI&lt; cells. Results led to the identification of C038 as a critical regulator of plasmacytoid dendritic cell function in response to influenza virus. Machine learning using study-derived clinical parameters and single-cell data effectively classified and predicted susceptibility to infection. The coordinated immune cell dynamics defined in this study provide a framework for identifying novel correlates of protection in the evaluation of future influenza therapeutics