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Summary: Background: Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. Methods: In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. Findings: 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 837 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0·32 [95% CI 0·27–0·37]) and 82% at 8 weeks (0·18 [0·14–0·23]) following the week in which significant changes in population movements were recorded. Interpretation: The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide. Funding: Wellcome Trust (UK), Robert Koch Institute (Germany), Federal Ministry of Health (Germany), Pfizer, Merck, Health Protection Surveillance Centre (Ireland), SpID-Net project (Ireland), European Centre for Disease Prevention and Control (European Union), Horizon 2020 (European Commission), Ministry of Health (Poland), National Programme of Antibiotic Protection (Poland), Ministry of Science and Higher Education (Poland), Agencia de Salut Pública de Catalunya (Spain), Sant Joan de Deu Foundation (Spain), Knut and Alice Wallenberg Foundation (Sweden), Swedish Research Council (Sweden), Region Stockholm (Sweden), Federal Office of Public Health of Switzerland (Switzerland), and French Public Health Agency (France).

As research and understanding of the cardiotoxic side-effects of anticancer therapy expands further and the affected patient population grows, notably the long-term survivors of childhood cancers, it is important to consider the full range of myocardial cell types affected. While the direct impacts of these toxins on cardiac myocytes constitute the most immediate damage, over the longer term, the myocardial ability to repair, or adapt to this damage becomes an ever greater component of the disease phenotype. One aspect is the potential for endogenous myocardial repair and renewal and how this may be limited by cardiotoxins depleting the cells that contribute to these processes. Clear evidence exists of new cardiomyocyte formation in adult human myocardium, along with the identification in the myocardium of endogenous stem/progenitor cell populations with pro-regenerative properties. Any effects of cardiotoxins on either of these processes will worsen long-term prognosis. While the role of cardiac stem/progenitor cells in cardiomyocyte renewal appears at best limited (although with stronger evidence of this process in response to diffuse cardiomyocyte loss), there are strong indications of a pro-regenerative function through the support of injured cell survival. A number of recent studies have identified detrimental impacts of anticancer therapies on cardiac stem/progenitor cells, with negative effects seen from both long-established chemotherapy agents such as, doxorubicin and from newer, less overtly cardiotoxic agents such as tyrosine kinase inhibitors. Damaging impacts are seen both directly, on cell numbers and viability, but also on these cells' ability to maintain the myocardium through generation of pro-survival secretome and differentiated cells. We here present a review of the identified impacts of cardiotoxins on cardiac stem and progenitor cells, considered in the context of the likely role played by these cells in the maintenance of myocardial tissue homeostasis.

The products of magnetic reconnection in Saturn’s magnetotail are identified in magnetometer observations primarily through characteristic deviations in the north–south component of the magnetic field. These magnetic deflections are caused by traveling plasma structures created during reconnection rapidly passing over the observing spacecraft. Identification of these signatures have long been performed by eye, and more recently through semi-automated methods, however these methods are often limited through a required human verification step. Here, we present a fully automated, supervised learning, feed forward neural network model to identify evidence of reconnection in the Kronian magnetosphere with the three magnetic field components observed by the Cassini spacecraft in Kronocentric radial–theta–phi coordinates as input. This model is constructed from a catalog of reconnection events which covers three years of observations with a total of 2093 classified events, categorized into plasmoids, traveling compression regions and dipolarizations. This neural network model is capable of rapidly identifying reconnection events in large time-span Cassini datasets, tested against the full year 2010 with a high level of accuracy (87%), true skill score (0.76), and Heidke skill score (0.73). From this model, a full cataloging and examination of magnetic reconnection events in the Kronian magnetosphere across Cassini's near Saturn lifetime is now possible.

When making decisions involving risk, people may learn about the risk from descriptions or from experience. The description-experience gap refers to the difference in decision patterns driven by this discrepancy in learning format. Across two experiments, we investigated whether learning from description versus experience differentially affects the direction and the magnitude of a context effect in risky decision making. In Study 1 and 2, a computerized game called the Decisions about Risk Task (DART) was used to measure people's risk-taking tendencies toward hazard stimuli that exploded probabilistically. The rate at which a context hazard caused harm was manipulated, while the rate at which a focal hazard caused harm was held constant. The format by which this information was learned was also manipulated; it was learned primarily by experience or by description. The results revealed that participants' behavior toward the focal hazard varied depending on what they had learned about the context hazard. Specifically, there were contrast effects in which participants were more likely to choose a risky behavior toward the focal hazard when the harm rate posed by the context hazard was high rather than low. Critically, these contrast effects were of similar strength irrespective of whether the risk information was learned from experience or description. Participants' verbal assessments of risk likelihood also showed contrast effects, irrespective of learning format. Although risk information about a context hazard in DART does nothing to affect the objective expected value of risky versus safe behaviors toward focal hazards, it did affect participants' perceptions and behaviors-regardless of whether the information was learned from description or experience. Our findings suggest that context has a broad-based role in how people assess and make decisions about hazards.

BackgroundIn patients with degenerative cervical myelopathy (DCM) that have spinal cord compression and sensorimotor deficits, surgical decompression is often performed. However, there is heterogeneity in clinical presentation and post-surgical functional recovery.ObjectivesPrimary: a) to assess differences in muscle fat infiltration (MFI) in patients with DCM versus controls, b) to assess association between MFI and clinical disability. Secondary: to assess association between MFI pre-surgery and post-surgical functional recovery.Study designCross-sectional case control study.MethodsEighteen patients with DCM (58.6 ± 14.2 years, 10 M/8F) and 25 controls (52.6 ± 11.8 years, 13M/12 F) underwent 3D Dixon fat-water imaging. A convolutional neural network (CNN) was used to segment cervical muscles (MFSS- multifidus and semispinalis cervicis, LC- longus capitis/colli) and quantify MFI. Modified Japanese Orthopedic Association (mJOA) and Nurick were collected.ResultsPatients with DCM had significantly higher MFI in MFSS (20.63 ± 5.43 vs 17.04 ± 5.24, p = 0.043) and LC (18.74 ± 6.7 vs 13.66 ± 4.91, p = 0.021) than controls. Patients with increased MFI in LC and MFSS had higher disability (LC: Nurick (Spearman's ρ = 0.436, p = 0.003) and mJOA (ρ = -0.399, p = 0.008)). Increased MFI in LC pre-surgery was associated with post-surgical improvement in Nurick (ρ = -0.664, p = 0.026) and mJOA (ρ = -0.603, p = 0.049).ConclusionIn DCM, increased muscle adiposity is significantly associated with sensorimotor deficits, clinical disability, and functional recovery after surgery. Accurate and time efficient evaluation of fat infiltration in cervical muscles may be conducted through implementation of CNN models.

Rhipidomys (Sigmodontinae, Thomasomyini) has 25 recognized species, with a wide distribution ranging from eastern Panama to northern Argentina. Cytogenetic data has been described for 13 species with 12 of them having 2n = 44 with a high level of autosomal fundamental number (FN) variation, ranging from 46 to 80, assigned to pericentric inversions. The species are grouped in groups with low FN (46-52) and high FN (72-80). In this work the karyotypes of Rhipidomys emiliae (2n = 44, FN = 50) and Rhipidomys mastacalis (2n = 44, FN = 74), were studied by classical cytogenetics and by fluorescence in situ hybridization using telomeric and whole chromosome probes (chromosome painting) of Hylaeamys megacephalus (HME). Chromosome painting revealed homology between 36 segments of REM and 37 of RMA. We tested the hypothesis that pericentric inversions are the predominant chromosomal rearrangements responsible for karyotypic divergence between these species, as proposed in literature. Our results show that the genomic diversification between the karyotypes of the two species resulted from translocations, centromeric repositioning and pericentric inversions. The chromosomal evolution in Rhipidomys was associated with karyotypical orthoselection. The HME probes revealed that seven syntenic probably ancestral blocks for Sigmodontinae are present in Rhipidomys. An additional syntenic block described here is suggested as part of the subfamily ancestral karyotype. We also define five synapomorphies that can be used as chromosomal signatures for Rhipidomys.

Abstract Rodents of the genus Cerradomys belong to the tribe Oryzomyini and present high chromosome variability with diploid numbers ranging from 2n=46 to 60. Classical cytogenetics and fluorescence in situ hybridization (FISH) with telomeric and whole chromosome-specific probes of another Oryzomyini, Oligoryzomys moojeni (OMO), were used to assess the karyotype evolution of the genus. Results were integrated into a molecular phylogeny to infer the hypothetical direction of chromosome changes. The telomeric FISH showed signals in telomeres in species that diverged early in the phylogeny, plus interstitial telomeric signals (ITS) in some species from the most derived clades (C. langguthi, C. vivoi, C. goytaca, and C. subflavus). Chromosome painting revealed homology from 23 segments of C. maracajuensis and C. marinhus to 32 of C. vivoi. Extensive chromosome reorganization was responsible for karyotypic differences in closely related species. Major drivers for genomic reshuffling were in tandem and centric fusion, fission, paracentric and pericentric inversions or centromere repositioning. Chromosome evolution was associated with an increase and decrease in diploid number in different lineages and ITS indicate remnants of ancient telomeres. Cytogenetics results corroborates that C. goytaca is not a junior synonym of C. subflavus since the karyotypic differences found may lead to reproductive isolation.

Previous studies have shown that epidural stimulation of the lumbosacral spinal cord (scES) can re-enable lower limb volitional motor control in individuals with chronic, clinically motor complete spinal cord injury (SCI). This observation entails that residual supraspinal connectivity to the lumbosacral spinal circuitry still persisted after SCI, although it was non-detectable when scES was not provided. In the present study, we aimed at exploring further the mechanisms underlying scES-promoted recovery of volitional lower limb motor control by investigating neuroimaging markers at the spinal cord lesion site via magnetic resonance imaging (MRI). Spinal cord MRI was collected prior to epidural stimulator implantation in 13 individuals with chronic, clinically motor complete SCI, and the spared tissue of specific regions of the spinal cord (anterior, posterior, right, left, and total cord) was assessed. After epidural stimulator implantation, and prior to any training, volitional motor control was evaluated during left and right lower limb flexion and ankle dorsiflexion attempts. The ability to generate force exertion and movement was not correlated to any neuroimaging marker. On the other hand, spared tissue of specific cord regions significantly and importantly correlated with some aspects of motor control that include activation amplitude of antagonist (negative correlation) muscles during left ankle dorsiflexion, and electromyographic coordination patterns during right lower limb flexion. The fact that amount and location of spared spinal cord tissue at the lesion site were not related to the ability to generate volitional lower limb movements may suggest that supraspinal inputs through spared spinal cord regions that differ across individuals can result in the generation of lower limb volitional motor output prior to any training when epidural stimulation is provided.

The widespread occurrence of pathogenic bacteria resistant to last-line antibiotics has resulted in significant challenges in human and veterinary medicine. There is an urgent need for new antimicrobial agents that can be used to control these life threating pathogens. We report the identification of antimicrobial activities, against a broad range of bacterial pathogens, from a collection of marine-derived spore-forming bacteria. Although marine environments have been previously investigated as sources of novel antibiotics, studies on such environments are still limited and there remain opportunities for further discoveries and this study has used resources derived from an under-exploited region, the Vietnam Sea. Antimicrobial activity was assessed against a panel of Gram-positive and Gram-negative bacteria, including several multi-drug resistant pathogens. From a total of 489 isolates, 16.4% had antimicrobial activity. Of 23 shortlisted isolates with the greatest antimicrobial activity, 22 were Bacillus spp. isolates and one was a Paenibacillus polymyxa isolate. Most of the antimicrobial compounds were sensitive to proteases, indicating that they were proteins rather than secondary metabolites. The study demonstrated that marine bacteria derived from the Vietnam Sea represent a rich resource, producing antimicrobial compounds with activity against a broad range of clinically relevant bacterial pathogens, including important antibiotic resistant pathogens. Several isolates were identified that have particularly broad range activities and produce antimicrobial compounds that may have value for future drug development.

BackgroundOccupational fatigue is a key issue in the rail industry that can endanger staff, passenger, and train safety. There is a need to demonstrate the relationship between workload, fatigue, and performance among rail staff.ObjectiveThe present study, conducted in the workplace in realistic situations, integrating both subjective and objective measurements, aimed at demonstrating the relationship between workload, fatigue, and cognitive performance with a rail staff sample.MethodsThe “After-Effect” technique was applied in the current study. Online diaries and cognitive performance tasks were used to assess the fatigue, work experiences, and performance of rail staff before and after work on the first and last days of one working week.ResultsReported fatigue was greater after work on both the first and last day of the working week. There were large individual differences in the change in fatigue and workload ratings. Analysis of covariance with age and the pre-work performance score as covariates and the post-work performance score as the dependent variable showed that high levels of fatigue were associated with impaired performance on both the visual search and logical reasoning tasks. Workload had fewer effects on performance than fatigue.ConclusionThis field study provided evidence for the relationship between work-related fatigue and performance impairment. The findings show the need for future work on predicting fatigue-related performance decrements, and the necessity of providing interventions and support so that the risk to safety can be reduced.

Lactiplantibacillus plantarum B21 isolated from Vietnamese sausage (nem chua) has previously displayed broad antimicrobial activity against Gram-positive bacteria including foodborne pathogens Listeria monocytogenes and Clostridium perfringens. This study successfully identified the antimicrobial agent as plantacyclin B21AG, a 5668 Da circular bacteriocin demonstrating high thermostability, resistance to a wide range of pH, proteolytic resistance and temporal stability. We report a reverse genetics approach to identify and characterise plantacyclin B21AG from first principles. The bacteriocin was purified from culture supernatant by a three-step process consisting of concentration, n-butanol extraction and cation exchange chromatography. A de novo peptide sequencing using LC-MS/MS techniques identified two putative peptide fragments which were mapped to the genome sequence of L. plantarum B21. This revealed an ORF corresponding to a putative circular bacteriocin with a 33-amino acid leader peptide and a 58-amino acid mature peptide encoded on a native plasmid pB21AG01. The bacteriocin is shown to be a small cationic predominantly α-helical protein (69%). The corresponding gene cluster, consisted of seven genes associated with post-translational circularisation, immunity and secretion. Whilst plantacyclin B21AG is 86% identical to the newly published plantaricyclin A it is more highly cationic having a net charge of +3 due to an additional basic residue in the putative membrane interaction region. This and other substitutions may well go some way to explaining functional differences. The robust nature of plantacyclin B21AG, its antimicrobial activity and associated machinery for cyclisation make it an interesting biotechnological target for development, both as a food-safe antimicrobial or potentially a platform technology for recombinant protein circularisation.

Aims and ObjectivesTo investigate how changes in the levels of preparedness and experiences of death and dying influence nursing students’ mental health.BackgroundThe COVID-19 pandemic is likely to cause significant trauma in the nursing population. The lack of preparation, in combination with a substantial loss of life, may have implications for the longer-term mental health of the nursing workforce. Nursing students have, in many cases, been an important part of the emergency response.DesignA longitudinal cohort study was conducted in the academic year 2014/15 with data collected at two time points. There was a 7-month time period between data collection.MethodsParticipants completed paper-based questionnaires measuring demographics, academic stressors, clinical stressors, and mental health. 358 nursing students at time point one and 347 at time point two (97% retention) completed the survey.ResultsInadequate preparation (OR: 1.783) and the inadequate preparation x death and dying interaction term (OR: 4.115) significantly increased risk of mental health problems over time. Increased death and dying alone did not increase mental health risk.ConclusionThe results of this study suggest that it is not the increase in death and dying per se that causes mental health difficulties, but that it is instead the experience of high levels of death and dying in combination with inadequate preparation. The data are considered within the context of the COVID-19 pandemic, with both inadequate preparation and the scale of death and dying being two significant stressors during the emergency period.

Myiopsitta monachus is a small Neotropical parrot (Psittaciformes: Arini Tribe) from subtropical and temperate regions of South America. It has a diploid chromosome number 2n = 48, different from other members of the Arini Tribe that have usually 70 chromosomes. The species has the lowest 2n within the Arini Tribe. In this study, we combined comparative chromosome painting with probes generated from chromosomes of Gallus gallus and Leucopternis albicollis, and FISH with bacterial artificial chromosomes (BACs) selected from the genome library of G. gallus with the aim to shed light on the dynamics of genome reorganization in M. monachus in the phylogenetic context. The homology maps showed a great number of fissions in macrochromosomes, and many fusions between microchromosomes and fragments of macrochromosomes. Our phylogenetic analysis by Maximum Parsimony agree with molecular data, placing M. monachus in a basal position within the Arini Tribe, together with Amazona aestiva (short tailed species). In M. monachus many chromosome rearrangements were found to represent autopomorphic characters, indicating that after this species split as an independent branch, an intensive karyotype reorganization took place. In addition, our results show that M. monachus probes generated by flow cytometry provide novel cytogenetic tools for the detection of avian chromosome rearrangements, since this species presents breakpoints that have not been described in other species.

Impulsivity and compulsivity are prominent non-motor problems in Parkinson’s disease (PD). Despite 20 years of research, there is still an ongoing debate as to whether subthalamic deep brain stimulation (STN DBS) for PD exacerbates or improves these symptoms. Here, we review how STN DBS affects clinical symptoms and neurocognitive aspects of impulsivity and compulsivity. When comparing patients post- to pre-surgery, in the majority of studies STN DBS for PD is associated with a decrease in clinically diagnosed impulse-control disorders and disorders of compulsivity. To avoid confounds, such as post-surgical decreases in dopaminergic medication doses, comparisons can also be made between DBS “On” versus “Off” conditions. These experimentally assayed effects of STN DBS with respect to neurocognitive aspects of impulsivity and compulsivity are more mixed. STN DBS improves behavioral flexibility without impairing negative feedback learning, delay discounting, or inhibitory control, as long as stimulation is restricted to the dorsal STN. However, STN DBS may drive impulsive actions when a subject is faced with competing choices. We discuss how motivated responses may be either enhanced or impaired by STN DBS depending on engagement of dorsal or ventral STN-mediated circuits. Future studies should combine structural and functional circuit measures with behavioral testing in PD patients on and off medication and stimulation. A more sophisticated understanding of how to modulate cortico-striatal-thalamo-cortical loops will increase the likelihood that these circuit manipulation techniques can successfully be applied to a wider range of neuropsychiatric disorders.

AIMS:To determine the cost and quality of life impact imposed by glaucoma in Tanzania, East Africa. METHODS:An expert panel of eye health professionals was convened to agree current glaucoma practice in Tanzania. In addition a structured patient survey was developed and administered. Supplemental cost and quality of life information was collected using cost questionnaires and validated quality of life measures, including the EQ5D and VFQ-25. RESULTS:Key findings include following. Non-adherence is a major issue, especially in rural settings where over 50% of the patients may fail to return for review. Whilst medical therapy is overwhelmingly the first line treatment, the cost of maintaining this represents up to 25% of a patient's income. There is an impact of glaucoma on patients general well-being as determined by the EQ-5D and more tellingly on visual function with particular impact on role limitations as determined by the VF25. Despite our sample being taken in a private clinic and thus containing a much larger proportion of professionals than the general population, one third of the population earned Tanzanian Shillings (TZS) 170,000 per month which is below the minimum wage. CONCLUSION:These findings are of great importance for health care planners seeking to determine cost-effective, acceptable methods of both identifying and treating this major cause of preventable blindness.

There is an increasing consumer demand for minimally processed, preservative free and microbiologically safe food. These factors, combined with risks of antibiotic resistance, have led to interest in bacteriocins produced by lactic acid bacteria (LAB) as natural food preservatives and as potential protein therapeutics. We previously reported the discovery of plantacyclin B21AG, a circular bacteriocin produced by Lactobacillus plantarum B21. Here, we describe the cloning and functional expression of the bacteriocin gene cluster in the probiotic Lactobacillus plantarum WCFS1. Genome sequencing demonstrated that the bacteriocin is encoded on a 20 kb native plasmid, designated as pB21AG01. Seven open reading frames (ORFs) putatively involved in bacteriocin production, secretion and immunity were cloned into an E. coli/Lactobacillus shuttle vector, pTRKH2. The resulting plasmid, pCycB21, was transformed into L. plantarum WCFS1. The cell free supernatants (CFS) of both B21 and WCFS1 (pCycB21) showed an antimicrobial activity of 800 AU/mL when tested against WCFS1 (pTRKH2) as the indicator strain, showing that functional expression of plantacyclin B21AG had been achieved. Real-time PCR analysis revealed that the relative copy number of pB21AG01 was 7.60 ± 0.79 in L. plantarum B21 whilst pCycB21 and pTRKH2 was 0.51 ± 0.05 and 25.19 ± 2.68 copies respectively in WCFS1. This indicates that the bacteriocin gene cluster is located on a highly stable low copy number plasmid pB21AG01 in L. plantarum B21. Inclusion of the native promoter for the bacteriocin operon from pB21AG01 results in similar killing activity being observed in both the wild type and recombinant hosts despite the lower copy number of pCycB21.

Here we present a secondary analysis from a parent database of 97 acutely injured participants enrolled in a prospective inception cohort study of whiplash recovery after motor vehicle collision (MVC). The purpose was to investigate the deep and superficial neck extensor muscles with peri-traumatic computed tomography (CT) and longitudinal measures of magnetic resonance imaging (MRI) in participants with varying levels of whiplash-related disability. Thirty-six underwent standard care imaging of the cervical spine with CT at a level-1 trauma designated emergency department. All 36 participants were assessed with MRI of the cervical spine at

The genus Oecomys (Rodentia, Sigmodontinae) is distributed from southern Central America to southeastern Brazil in South America. It currently comprises 18 species, but multidisciplinary approaches such as karyotypic, morphological and molecular studies have shown that there is a greater diversity within some lineages than others. In particular, it has been proposed that O. paricola constitutes a species complex with three evolutionary units, which have been called the northern, eastern and western clades. Aiming to clarify the taxonomic status of O. paricola and determine the relevant chromosomal rearrangements, we investigated the karyotypes of samples from eastern Amazonia by chromosomal banding and FISH with Hylaeamys megacephalus (HME) whole-chromosome probes. We detected three cytotypes for O. paricola: A (OPA-A; 2n = 72, FN = 75), B (OPA-B; 2n = 70, FN = 75) and C (OPA-C; 2n = 70, FN = 72). Comparative chromosome painting showed that fusions/fissions, translocations and pericentric inversions or centromeric repositioning were responsible for the karyotypic divergence. We also detected exclusive chromosomal signatures that can be used as phylogenetic markers. Our analysis of karyotypic and distribution information indicates that OPA-A, OPA-B and OPA-C are three distinct species that belong to the eastern clade, with sympatry occurring between two of them, and that the "paricola group" is more diverse than was previously thought.

Abstract Background Diffusion-weighted magnetic resonance imaging (DW-MRI) of skeletal muscle has the potential to be a sensitive diagnostic and/or prognostic tool in complex, enigmatic neuromusculoskeletal conditions such as spinal cord injury and whiplash associated disorder. However, the reliability and reproducibility of clinically accessible DW-MRI parameters in skeletal muscle remains incompletely characterized – even in individuals without neuromusculoskeletal injury – and these parameters have yet to be characterized for many clinical populations. Here, we provide normative measures of the apparent diffusion coefficient (ADC) in healthy muscles of the lower limb; assess the rater-based reliability and short- and long-term reproducibility of the ADC in the same muscles; and quantify ADC of these muscles in individuals with motor incomplete spinal cord injury. Methods Twenty individuals without neuromusculoskeletal injury and 14 individuals with motor incomplete spinal cord injury (SCI) participated in this investigation. We acquired bilateral diffusion-weighted MRI of the lower limb musculature in all participants at 3 T using a multi-shot echo-planar imaging sequence with b-values of 0, 100, 300 and 500 s/mm2 and diffusion-probing gradients applied in 3 orthogonal directions. Outcome measures included: (1) average ADC in the lateral and medial gastrocnemius, tibialis anterior, and soleus of individuals without neurological or musculoskeletal injury; (2) intra- and inter-rater reliability, as well as short and long-term reproducibility of the ADC; and (3) estimation of average muscle ADC in individuals with SCI. Results Intra- and inter-rater reliability of the ADC averaged 0.89 and 0.79, respectively, across muscles. Least significant change, a measure of temporal reproducibility, was 4.50 and 11.98% for short (same day) and long (9-month) inter-scan intervals, respectively. Average ADC was significantly elevated across muscles in individuals with SCI compared to individuals without neurological or musculoskeletal injury (1.655 vs. 1.615 mm2/s, respectively). Conclusions These findings provide a foundation for future studies that track longitudinal changes in skeletal muscle ADC of the lower extremity and/or investigate the mechanisms underlying ADC changes in cases of known or suspected pathology.

Metal–organic framework glasses have emerged as a new family of melt-quenched glass, but have yet to display the accessible porosity of their crystalline counterparts. Here, Bennett and colleagues report that glasses derived from ZIF-76 parent materials possess 4 – 8 Å pores and exhibit reversible gas adsorption.

FISH-based techniques to image and count mRNA in single cells can be limited by the photophysical properties of organic dyes. Here the authors develop photostable quantum dot FISH probes for multiplexed imaging.

Abstract Background Several independent research groups have shown that alterations in human sperm methylation profiles correlate with decreased fecundity and an increased risk of poor embryo development. Moving these initial findings from the lab into a clinical setting where they can be used to measure male infertility though requires a platform that is stable and robust against batch effects that can occur between sample runs. Operating parameters must be established, performance characteristics determined, and guidelines set to ensure repeatability and accuracy. The standard for technical validation of a lab developed test (LDT) in the USA comes from the Clinical Laboratory Improvement Amendments (CLIA). However, CLIA was introduced in 1988, before the advent of genome-wide profiling and associated computational analysis. This, coupled with its intentionally general nature, makes its interpretation for epigenetic assays non-trivial. Results Here, we present an interpretation of the CLIA technical validation requirements for profiling DNA methylation and calling aberrant methylation using the Illumina Infinium platform (e.g., the 450HM and MethylationEPIC). We describe an experimental design to meet these requirements, the experimental results obtained, and the operating parameters established. Conclusions The CLIA guidelines, although not intended for high-throughput assays, can be interpreted in a way that is consistent with modern epigenetic assays. Based on such an interoperation, Illumina’s Infinium platform is quite amenable to usage in a clinical setting for diagnostic work.

Abstract Short tandem repeats (STRs), also known as microsatellites, are commonly used to noninvasively genotype wild‐living endangered species, including African apes. Until recently, capillary electrophoresis has been the method of choice to determine the length of polymorphic STR loci. However, this technique is labor intensive, difficult to compare across platforms, and notoriously imprecise. Here we developed a MiSeq‐based approach and tested its performance using previously genotyped fecal samples from long‐term studied chimpanzees in Gombe National Park, Tanzania. Using data from eight microsatellite loci as a reference, we designed a bioinformatics platform that converts raw MiSeq reads into locus‐specific files and automatically calls alleles after filtering stutter sequences and other PCR artifacts. Applying this method to the entire Gombe population, we confirmed previously reported genotypes, but also identified 31 new alleles that had been missed due to sequence differences and size homoplasy. The new genotypes, which increased the allelic diversity and heterozygosity in Gombe by 61% and 8%, respectively, were validated by replicate amplification and pedigree analyses. This demonstrated inheritance and resolved one case of an ambiguous paternity. Using both singleplex and multiplex locus amplification, we also genotyped fecal samples from chimpanzees in the Greater Mahale Ecosystem in Tanzania, demonstrating the utility of the MiSeq‐based approach for genotyping nonhabituated populations and performing comparative analyses across field sites. The new automated high‐throughput analysis platform (available at https://github.com/ShawHahnLab/chiimp) will allow biologists to more accurately and effectively determine wildlife population size and structure, and thus obtain information critical for conservation efforts.

The recently introduced glass and liquid states of metal–organic frameworks (MOFs) provide opportunities to design and explore new properties for this class of material. Here, the authors show that a MOF liquid can be blended with another MOF component to produce domain-structured MOF glasses with single, tailorable glass transitions.

Quantum dots (QDs) mimic delivery agents for drugs and analytic compounds, but which route do they take inside cells? Here, the authors developed a technique to follow QDs, and they show that zwitterionic nanoparticle surface coatings make for the best delivery vehicle.

Abstract Background The family Phyllostomidae (Chiroptera) shows wide morphological, molecular and cytogenetic variation; many disagreements regarding its phylogeny and taxonomy remains to be resolved. In this study, we use chromosome painting with whole chromosome probes from the Phyllostomidae Phyllostomus hastatus and Carollia brevicauda to determine the rearrangements among several genera of the Nullicauda group (subfamilies Gliphonycterinae, Carolliinae, Rhinophyllinae and Stenodermatinae). Results These data, when compared with previously published chromosome homology maps, allow the construction of a phylogeny comparable to those previously obtained by morphological and molecular analysis. Our phylogeny is largely in agreement with that proposed with molecular data, both on relationships between the subfamilies and among genera; it confirms, for instance, that Carollia and Rhinophylla, previously considered as part of the same subfamily are, in fact, distant genera. Conclusions The occurrence of the karyotype considered ancestral for this family in several different branches suggests that the diversification of Phyllostomidae into many subfamilies has occurred in a short period of time. Finally, the comparison with published maps using human whole chromosome probes allows us to track some syntenic associations prior to the emergence of this family.

The Demand Resources and Individual Effects Model (DRIVE Model) is a transactional model that integrates Demands- Control-Support and Effort-Reward Imbalance models emphasising the role of individual (Coping Strategies; Overcommitment) and job characteristics (Job Demands, Social Support, Decision Latitude, Skill Discretion, Effort, Rewards) in the work-related stress process. The present study aimed to test the DRIVE Model in a sample of 450 Italian nurses and to compare findings with those of a study conducted in a sample of UK nurses. A questionnaire composed of Ways of Coping Checklist-Revised (WCCL-R); Job Content Questionnaire (JCQ); ERI Test; Hospital Anxiety and Depression Scale (HADS) was used. Data supported the application of the DRIVE Model to the Italian context, showing significant associations of the individual characteristics of Problem-focused, Seek Advice and Wishful Thinking coping strategies and the job characteristics of Job Demands, Skill Discretion, Decision Latitude, and Effort with perceived levels of Anxiety and Depression. Effort represented the best predictor for psychological health conditions among Italian nurses, and Social Support significantly moderated the effects of Job Demands on perceived levels of Anxiety. The comparison study showed significant differences in the risk profiles of Italian and UK nurses. Findings were discussed in order to define focused interventions to promote nurses’ wellbeing.

Abstract High-throughput RNA-sequencing (RNA-seq) technologies provide an unprecedented opportunity to explore the individual transcriptome. Unmapped reads are a large and often overlooked output of standard RNA-seq analyses. Here, we present Read Origin Protocol (ROP), a tool for discovering the source of all reads originating from complex RNA molecules. We apply ROP to samples across 2630 individuals from 54 diverse human tissues. Our approach can account for 99.9% of 1 trillion reads of various read length. Additionally, we use ROP to investigate the functional mechanisms underlying connections between the immune system, microbiome, and disease. ROP is freely available at https://github.com/smangul1/rop/wiki.