A quantum coherent spin in hexagonal boron nitride at ambient conditions.

Solid-state spin-photon interfaces that combine single-photon generation and long-lived spin coherence with scalable device integration-ideally under ambient conditions-hold great promise for the implementation of quantum networks and sensors. Despite rapid progress reported across several candidate systems, those possessing quantum coherent single spins at room temperature remain extremely rare. Here we report quantum coherent control under ambient conditions of a single-photon-emitting defect spin in a layered van der Waals material, namely, hexagonal boron nitride. We identify that the carbon-related defect has a spin-triplet electronic ground-state manifold. We demonstrate that the spin coherence is predominantly governed by coupling to only a few proximal nuclei and is prolonged by decoupling protocols. Our results serve to introduce a new platform to realize a room-temperature spin qubit coupled to a multiqubit quantum register or quantum sensor with nanoscale sample proximity.

Interspecies Transmission of Swine Influenza A Viruses and Human Seasonal Vaccine-Mediated Protection Investigated in Ferret Model.

We investigated the infection dynamics of 2 influenza A(H1N1) virus isolates from the swine 1A.3.3.2 (pandemic 2009) and 1C (Eurasian, avian-like) lineages. The 1C-lineage virus, A/Pavia/65/2016, although phylogenetically related to swine-origin viruses, was isolated from a human clinical case. This strain infected ferrets, a human influenza model species, and could be transmitted by direct contact and, less efficiently, by airborne exposure. Infecting ferrets and pigs (the natural host) resulted in mild or inapparent clinical signs comparable to those observed with 1A.3.3.2-lineage swine-origin viruses. Both H1N1 viruses could infect pigs and were transmitted to cohoused ferrets. Ferrets vaccinated with a human 2016-17 seasonal influenza vaccine were protected against infection with the antigenically matched 1A pandemic 2009 virus but not against the swine-lineage 1C virus. Our results reaffirm the need for continuous influenza A virus surveillance in pigs and identification of candidate human vaccine viruses.

Excited State Spectroscopy of Boron Vacancy Defects in Hexagonal Boron Nitride Using Time-Resolved Optically Detected Magnetic Resonance.

We report optically detected magnetic resonance (ODMR) measurements of an ensemble of spin-1 negatively charged boron vacancies in hexagonal boron nitride. The photoluminescence decay rates are spin-dependent, with intersystem crossing rates of 1.02 ns-1 and 2.03 ns-1 for the mS = 0 and mS = ±1 states, respectively. Time gating the photoluminescence enhances the ODMR contrast by discriminating between different decay rates. This is particularly effective for detecting the spin of the optically excited state, where a zero-field splitting of |DES| = 2.09 GHz is measured. The magnetic field dependence of the photoluminescence exhibits dips corresponding to the ground (GSLAC) and excited-state (ESLAC) anticrossings and additional anticrossings due to coupling with nearby spin-1/2 parasitic impurities. Comparison to a model suggests that the anticrossings are mediated by the interaction with nuclear spins and allows an estimate of the ratio of the singlet to triplet spin-dependent relaxation rates of κ0/κ1 = 0.34.

Vaccines That Reduce Viral Shedding Do Not Prevent Transmission of H1N1 Pandemic 2009 Swine Influenza A Virus Infection to Unvaccinated Pigs.

Swine influenza A virus (swIAV) infection causes substantial economic loss and disease burden in humans and animals. The 2009 pandemic H1N1 (pH1N1) influenza A virus is now endemic in both populations. In this study, we evaluated the efficacy of different vaccines in reducing nasal shedding in pigs following pH1N1 virus challenge. We also assessed transmission from immunized and challenged pigs to naive, directly in-contact pigs. Pigs were immunized with either adjuvanted, whole inactivated virus (WIV) vaccines or virus-vectored (ChAdOx1 and MVA) vaccines expressing either the homologous or heterologous influenza A virus hemagglutinin (HA) glycoprotein, as well as an influenza virus pseudotype (S-FLU) vaccine expressing heterologous HA. Only two vaccines containing homologous HA, which also induced high hemagglutination inhibitory antibody titers, significantly reduced virus shedding in challenged animals. Nevertheless, virus transmission from challenged to naive, in-contact animals occurred in all groups, although it was delayed in groups of vaccinated animals with reduced virus shedding.IMPORTANCE This study was designed to determine whether vaccination of pigs with conventional WIV or virus-vectored vaccines reduces pH1N1 swine influenza A virus shedding following challenge and can prevent transmission to naive in-contact animals. Even when viral shedding was significantly reduced following challenge, infection was transmissible to susceptible cohoused recipients. This knowledge is important to inform disease surveillance and control strategies and to determine the vaccine coverage required in a population, thereby defining disease moderation or herd protection. WIV or virus-vectored vaccines homologous to the challenge strain significantly reduced virus shedding from directly infected pigs, but vaccination did not completely prevent transmission to cohoused naive pigs.

Ranking microbial metabolomic and genomic links in the NPLinker framework using complementary scoring functions.

Specialised metabolites from microbial sources are well-known for their wide range of biomedical applications, particularly as antibiotics. When mining paired genomic and metabolomic data sets for novel specialised metabolites, establishing links between Biosynthetic Gene Clusters (BGCs) and metabolites represents a promising way of finding such novel chemistry. However, due to the lack of detailed biosynthetic knowledge for the majority of predicted BGCs, and the large number of possible combinations, this is not a simple task. This problem is becoming ever more pressing with the increased availability of paired omics data sets. Current tools are not effective at identifying valid links automatically, and manual verification is a considerable bottleneck in natural product research. We demonstrate that using multiple link-scoring functions together makes it easier to prioritise true links relative to others. Based on standardising a commonly used score, we introduce a new, more effective score, and introduce a novel score using an Input-Output Kernel Regression approach. Finally, we present NPLinker, a software framework to link genomic and metabolomic data. Results are verified using publicly available data sets that include validated links.

Prebiotic amino acids bind to and stabilize prebiotic fatty acid membranes.

The membranes of the first protocells on the early Earth were likely self-assembled from fatty acids. A major challenge in understanding how protocells could have arisen and withstood changes in their environment is that fatty acid membranes are unstable in solutions containing high concentrations of salt (such as would have been prevalent in early oceans) or divalent cations (which would have been required for RNA catalysis). To test whether the inclusion of amino acids addresses this problem, we coupled direct techniques of cryoelectron microscopy and fluorescence microscopy with techniques of NMR spectroscopy, centrifuge filtration assays, and turbidity measurements. We find that a set of unmodified, prebiotic amino acids binds to prebiotic fatty acid membranes and that a subset stabilizes membranes in the presence of salt and Mg2+ Furthermore, we find that final concentrations of the amino acids need not be high to cause these effects; membrane stabilization persists after dilution as would have occurred during the rehydration of dried or partially dried pools. In addition to providing a means to stabilize protocell membranes, our results address the challenge of explaining how proteins could have become colocalized with membranes. Amino acids are the building blocks of proteins, and our results are consistent with a positive feedback loop in which amino acids bound to self-assembled fatty acid membranes, resulting in membrane stabilization and leading to more binding in turn. High local concentrations of molecular building blocks at the surface of fatty acid membranes may have aided the eventual formation of proteins.

Comparative Metabologenomics Analysis of Polar Actinomycetes.

Biosynthetic and chemical datasets are the two major pillars for microbial drug discovery in the omics era. Despite the advancement of analysis tools and platforms for multi-strain metabolomics and genomics, linking these information sources remains a considerable bottleneck in strain prioritisation and natural product discovery. In this study, molecular networking of the 100 metabolite extracts derived from applying the OSMAC approach to 25 Polar bacterial strains, showed growth media specificity and potential chemical novelty was suggested. Moreover, the metabolite extracts were screened for antibacterial activity and promising selective bioactivity against drug-persistent pathogens such as Klebsiella pneumoniae and Acinetobacter baumannii was observed. Genome sequencing data were combined with metabolomics experiments in the recently developed computational approach, NPLinker, which was used to link BGC and molecular features to prioritise strains for further investigation based on biosynthetic and chemical information. Herein, we putatively identified the known metabolites ectoine and chrloramphenicol which, through NPLinker, were linked to their associated BGCs. The metabologenomics approach followed in this study can potentially be applied to any large microbial datasets for accelerating the discovery of new (bioactive) specialised metabolites.

Optical Gating of Photoluminescence from Color Centers in Hexagonal Boron Nitride.

We report on multicolor excitation experiments with color centers in hexagonal boron nitride at cryogenic temperatures. We demonstrate controllable optical switching between bright and dark states of color centers emitting around 2 eV. Resonant, or quasi-resonant, excitation of photoluminescence also pumps the color center, via a two-photon process, into a dark state, where it becomes trapped. Repumping back into the bright state has a step-like spectrum with a defect-dependent threshold between 2.25 and 2.6 eV. This behavior is consistent with photoionization and charging between optically bright and dark states of the defect. Furthermore, a second zero phonon line, detuned by +0.4 eV, is observed in absorption with orthogonal polarization to the emission, evidencing an additional energy level in the color center.

Towards harmonization of microscopy methods for malaria clinical research studies.

Microscopy performed on stained films of peripheral blood for detection, identification and quantification of malaria parasites is an essential reference standard for clinical trials of drugs, vaccines and diagnostic tests for malaria. The value of data from such research is greatly enhanced if this reference standard is consistent across time and geography. Adherence to common standards and practices is a prerequisite to achieve this. The rationale for proposed research standards and procedures for the preparation, staining and microscopic examination of blood films for malaria parasites is presented here with the aim of improving the consistency and reliability of malaria microscopy performed in such studies. These standards constitute the core of a quality management system for clinical research studies employing microscopy as a reference standard. They can be used as the basis for the design of training and proficiency testing programmes as well as for procedures and quality assurance of malaria microscopy in clinical research.

Nuclear lamina defects cause ATM-dependent NF-κB activation and link accelerated aging to a systemic inflammatory response.

Alterations in the architecture and dynamics of the nuclear lamina have a causal role in normal and accelerated aging through both cell-autonomous and systemic mechanisms. However, the precise nature of the molecular cues involved in this process remains incompletely defined. Here we report that the accumulation of prelamin A isoforms at the nuclear lamina triggers an ATM- and NEMO-dependent signaling pathway that leads to NF-κB activation and secretion of high levels of proinflammatory cytokines in two different mouse models of accelerated aging (Zmpste24(-/-) and Lmna(G609G/G609G) mice). Causal involvement of NF-κB in accelerated aging was demonstrated by the fact that both genetic and pharmacological inhibition of NF-κB signaling prevents age-associated features in these animal models, significantly extending their longevity. Our findings provide in vivo proof of principle for the feasibility of pharmacological modulation of the NF-κB pathway to slow down the progression of physiological and pathological aging.

Predictive value of C-reactive protein for tuberculosis, bloodstream infection or death among HIV-infected individuals with chronic, non-specific symptoms and negative sputum smear microscopy.

BACKGROUND: C-reactive protein (CRP) is an inflammatory biomarker that may identify patients at risk of infections or death. Mortality among HIV-infected persons commencing antiretroviral therapy (ART) is often attributed to tuberculosis (TB) or bloodstream infections (BSI). METHODS: In two district hospitals in southern Malawi, we recruited HIV-infected adults with one or more unexplained symptoms present for at least one month (weight loss, fever or diarrhoea) and negative expectorated sputum microscopy for TB. CRP determination for 452 of 469 (96%) participants at study enrolment was analysed for associations with TB, BSI or death to 120 days post-enrolment. RESULTS: Baseline CRP was significantly elevated among patients with confirmed or probable TB (52), BSI (50) or death (60) compared to those with no identified infection who survived at least 120 days (269). A CRP value of >10 mg/L was associated with confirmed or probable TB (adjusted odds ratio 5.7; 95% CI 2.6, 14.3; 87% sensitivity) or death by 30 days (adjusted odds ratio 9.2; 95% CI 2.2, 55.1; 88% sensitivity). CRP was independently associated with TB, BSI or death, but the prediction of these endpoints was enhanced by including haemoglobin (all outcomes), CD4 count (BSI, death) and whether ART was started (death) in logistic regression models. CONCLUSION: High CRP at the time of ART initiation is associated with TB, BSI and early mortality and so has potential utility for stratifying patients for intensified clinical and laboratory investigation and follow-up. They may also be considered for empirical treatment of opportunistic infections including TB.

Mutations in CHD2 cause defective association with active chromatin in chronic lymphocytic leukemia.

Great progress has recently been achieved in the understanding of the genomic alterations driving chronic lymphocytic leukemia (CLL). Nevertheless, the specific molecular mechanisms governing chromatin remodeling in CLL are unknown. Here we report the genetic and functional characterization of somatic mutations affecting the chromatin remodeler CHD2, one of the most frequently mutated genes in CLL (5.3%) and in monoclonal B lymphocytosis (MBL, 7%), a B-cell expansion that can evolve to CLL. Most of the mutations affecting CHD2, identified by whole-exome sequencing of 456 CLL and 43 MBL patients, are either truncating or affect conserved residues in functional domains, thus supporting a putative role for CHD2 as a tumor suppressor gene. CHD2 mutants show altered nuclear distribution, and a chromodomain helicase DNA binding protein 2 (CHD2) mutant affected in its DNA-binding domain exhibits defective association with active chromatin. Clinicobiological analyses show that most CLL patients carrying CHD2 mutations also present mutated immunoglobulin heavy chain variable region genes (IGHVs), being the most frequently mutated gene in this prognostic subgroup. This is the first study providing functional evidence supporting CHD2 as a cancer driver and opens the way to further studies of the role of this chromatin remodeler in CLL.

Defect-Free Self-Catalyzed GaAs/GaAsP Nanowire Quantum Dots Grown on Silicon Substrate.

The III-V nanowire quantum dots (NWQDs) monolithically grown on silicon substrates, combining the advantages of both one- and zero-dimensional materials, represent one of the most promising technologies for integrating advanced III-V photonic technologies on a silicon microelectronics platform. However, there are great challenges in the fabrication of high-quality III-V NWQDs by a bottom-up approach, that is, growth by the vapor-liquid-solid method, because of the potential contamination caused by external metal catalysts and the various types of interfacial defects introduced by self-catalyzed growth. Here, we report the defect-free self-catalyzed III-V NWQDs, GaAs quantum dots in GaAsP nanowires, on a silicon substrate with pure zinc blende structure for the first time. Well-resolved excitonic emission is observed with a narrow line width. These results pave the way toward on-chip III-V quantum information and photonic devices on silicon platform.

Factors Underlying Ebola Virus Infection Among Health Workers, Kenema, Sierra Leone, 2014-2015.

BACKGROUND: Ebola virus disease (EVD) in health workers (HWs) has been a major challenge during the 2014-2015 outbreak. We examined factors associated with Ebola virus exposure and mortality in HWs in Kenema District, Sierra Leone. METHODS: We analyzed data from the Sierra Leone National Viral Hemorrhagic Fever Database, contact tracing records, Kenema Government Hospital (KGH) staff and Ebola Treatment Unit (ETU) rosters, and burial logs. RESULTS: From May 2014 through January 2015, 600 cases of EVD originated in Kenema District, including 92 (15%) HWs, 66 (72%) of whom worked at KGH. Among KGH medical staff and international volunteers, 18 of 62 (29%) who worked in the ETU developed EVD, compared with 48 of 83 (58%) who worked elsewhere in the hospital. Thirteen percent of HWs with EVD reported contact with EVD patients, while 27% reported contact with other infected HWs. The number of HW EVD cases at KGH declined roughly 1 month after implementation of a new triage system at KGH and the opening of a second ETU within the district. The case fatality ratio for HWs and non-HWs with EVD was 69% and 74%, respectively. CONCLUSIONS: The cluster of HW EVD cases in Kenema District is one of the largest ever reported. Most HWs with EVD had potential virus exposure both inside and outside of hospitals. Prevention measures for HWs must address a spectrum of infection risks in both formal and informal care settings as well as in the community.

Loss of mitochondrial protease OMA1 alters processing of the GTPase OPA1 and causes obesity and defective thermogenesis in mice.

Mitochondria are dynamic subcellular organelles that convert nutrient intermediates into readily available energy equivalents. Optimal mitochondrial function is ensured by a highly evolved quality control system, coordinated by protein machinery that regulates a process of continual fusion and fission. In this work, we provide in vivo evidence that the ATP-independent metalloprotease OMA1 plays an essential role in the proteolytic inactivation of the dynamin-related GTPase OPA1 (optic atrophy 1). We also show that OMA1 deficiency causes a profound perturbation of the mitochondrial fusion-fission equilibrium that has important implications for metabolic homeostasis. Thus, ablation of OMA1 in mice results in marked transcriptional changes in genes of lipid and glucose metabolic pathways and substantial alterations in circulating blood parameters. Additionally, Oma1-mutant mice exhibit an increase in body weight due to increased adipose mass, hepatic steatosis, decreased energy expenditure and impaired thermogenenesis. These alterations are especially significant under metabolic stress conditions, indicating that an intact OMA1-OPA1 system is essential for developing the appropriate adaptive response to different metabolic stressors such as a high-fat diet or cold-shock. This study provides the first description of an unexpected role in energy metabolism for the metalloprotease OMA1 and reinforces the importance of mitochondrial quality control for normal metabolic function.

Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance.

BACKGROUND: Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance. METHODS: To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods. RESULTS: The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites. CONCLUSIONS: Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel resistance mutations to improve the design of tuberculosis control measures, such as diagnostics, and inform patient management.

Matriptase-2 is essential for hepcidin repression during fetal life and postnatal development in mice to maintain iron homeostasis.

Iron is an essential element required for development and survival of all living organisms. In fetuses, maternofetal iron transfer across the placenta is essential for growth and development. In neonates, efficient intestinal iron absorption is required to scavenge as much iron as possible from the low-iron-content milk. During these periods, efficient iron mobilization is ensured by the downregulation of the iron regulatory hormone hepcidin by as-yet uncharacterized molecular mechanisms. Here we demonstrate that the recently described hepcidin repressor-the serine protease matriptase-2 (encoded by Tmprss6)-is responsible for this repression throughout development, with its deficiency leading to increased hepcidin levels triggering iron deficiency and anemia starting in utero. This result might have implications for a better understanding of iron homeostasis during early development in iron-refractory iron deficiency anemia patients, who present with microcytic anemia caused by hyperhepcidinemia, and of questions about the role of matriptase-2 in human neonates.

Reporting guidelines for implementation and operational research.

In public health, implementation research is done to improve access to interventions that have been shown to work but have not reached many of the people who could benefit from them. Researchers identify practical problems facing public health programmes and aim to find solutions that improve health outcomes. In operational research, routinely-collected programme data are used to uncover ways of delivering more effective, efficient and equitable health care. As implementation research can address many types of questions, many research designs may be appropriate. Existing reporting guidelines partially cover the methods used in implementation and operational research, so we ran a consultation through the World Health Organization (WHO), the Alliance for Health Policy & Systems Research (AHPSR) and the Special Programme for Research and Training in Tropical Diseases (TDR) and developed guidelines to facilitate the funding, conduct, review and publishing of such studies. Our intention is to provide a practical reference for funders, researchers, policymakers, implementers, reviewers and editors working with implementation and operational research. This is an evolving field, so we plan to monitor the use of these guidelines and develop future versions as required.

Dans le domaine de la santé publique, des recherches sur la mise en œuvre sont menées pour améliorer l'accès aux interventions qui se sont révélées efficaces, mais qui n'ont pas touché toutes les personnes qui auraient pu en bénéficier. Les chercheurs identifient les difficultés pratiques qui compromettent les programmes de santé publique et s'efforcent de trouver des solutions pour améliorer les résultats sanitaires. Les données de programme systématiquement collectées dans le cadre des recherches opérationnelles, sont utilisées pour mettre en lumière des moyens de rendre les soins de santé plus efficaces, efficients et équitables. D'autre part, comme il est possible que les recherches sur la mise en œuvre portent sur de nombreux types de questions, différents plans de recherche peuvent s'avérer appropriés. Les directives existantes concernant l'établissement de rapports traitent en partie des méthodes utilisées dans le cadre des recherches sur la mise en œuvre et des recherches opérationnelles. Nous avons donc mené une consultation au sein de l'Organisation mondiale de la Santé (OMS), de l'Alliance pour la recherche sur les politiques et les systèmes de santé (AHPSR) et du Programme spécial de recherche et de formation concernant les maladies tropicales (TDR) et élaboré des directives pour faciliter le financement, la conduite, la révision et la publication de ce type de recherches. Notre objectif est de fournir une référence pratique pour les bailleurs de fonds, les chercheurs, les décideurs, les responsables de la mise en œuvre, les réviseurs et les éditeurs associés aux recherches sur la mise en œuvre et aux recherches opérationnelles. Ce domaine étant en constante évolution, nous prévoyons de suivre l'utilisation de ces directives et de rédiger, si besoin est, de futures versions.

En la salud pública, las investigaciones sobre la ejecución se llevan a cabo para mejorar el acceso a las intervenciones que se ha demostrado que funcionan pero que no han llegado a una gran parte de las personas que podrían beneficiarse de ellas. Los investigadores identifican los problemas prácticos a los que se enfrentan los programas de salud pública y tratan de encontrar soluciones que mejoren los resultados sanitarios. En las investigaciones operativas, se utilizan datos de programas recopilados rutinariamente para descubrir formas de ofrecer una atención sanitaria más efectiva, eficiente y equitativa. Puesto que una investigación sobre la ejecución puede abordar muchos tipos de cuestiones, pueden ser apropiados muchos diseños de investigación. Las directrices existentes sobre la presentación de informes cubren parcialmente los métodos utilizados en las investigaciones operativas y sobre la ejecución, por lo que se llevó a cabo una consulta a través de la Organización Mundial de la Salud (OMS), la Alianza para la Investigación en Políticas y Sistemas de Salud (Alianza IPSS) y el Programa Especial de Investigaciones y Enseñanzas sobre Enfermedades Tropicales (TDR) y se desarrollaron directrices para facilitar la financiación, realización, revisión y publicación de dichos estudios. El objetivo es proporcionar una referencia práctica para financiadores, investigadores, responsables de la formulación de políticas, implementadores, revisores y editores que trabajen con investigaciones operativas y sobre la ejecución. Se trata de un área en evolución, por lo que prevemos supervisar el uso de estas directrices y desarrollar versiones futuras si fuera necesario.

Increasing physical activity in stroke survivors using STARFISH, an interactive mobile phone application: a pilot study.

BACKGROUND: Following stroke, people are generally less active and more sedentary which can worsen outcomes. Mobile phone applications (apps) can support change in health behaviors. We developed STARFISH, a mobile phone app-based intervention, which incorporates evidence-based behavior change techniques (feedback, self-monitoring and social support), in which users' physical activity is visualized by fish swimming. OBJECTIVE: To evaluate the potential effectiveness of STARFISH in stroke survivors. METHOD: Twenty-three people with stroke (12 women; age: 56.0 ± 10.0 years, time since stroke: 4.2 ± 4.0 years) from support groups in Glasgow completed the study. Participants were sequentially allocated in a 2:1 ratio to intervention (n = 15) or control (n = 8) groups. The intervention group followed the STARFISH program for six weeks; the control group received usual care. Outcome measures included physical activity, sedentary time, heart rate, blood pressure, body mass index, Fatigue Severity Scale, Instrumental Activity of Daily Living Scale, Ten-Meter Walk Test, Stroke Specific Quality of Life Scale, and Psychological General Well-Being Index. RESULTS: The average daily step count increased by 39.3% (4158 to 5791 steps/day) in the intervention group and reduced by 20.2% (3694 to 2947 steps/day) in the control group (p = 0.005 for group-time interaction). Similar patterns of data and group-time interaction were seen for walking time (p = 0.002) and fatigue (p = 0.003). There were no significant group-time interactions for other outcome measures. CONCLUSION: Use of STARFISH has the potential to improve physical activity and health outcomes in people after stroke and longer term intervention trials are warranted.

Functional analysis of sucrase-isomaltase mutations from chronic lymphocytic leukemia patients.

Next-generation sequencing techniques have emerged as powerful tools for the understanding of cancer genomes. In recent years, whole-exome and whole-genome sequencing strategies have enabled the annotation of a comprehensive mutation landscape of chronic lymphocytic leukemia (CLL), the most frequent leukemia in western countries. Several recurrently mutated genes have been identified, with a subset being validated as neoplastic drivers. Still, a main challenge remains for the differentiation between driver and passenger mutations among candidates as well as for the functional description of the newly discovered leukemogenic genes that could be utilized for personalized anti-tumor strategies. In this scenario, we have identified the metabolic enzyme sucrase-isomaltase (SI) as one of the most frequently mutated genes in a cohort of 105 CLL patients. Here, we demonstrate that these SI mutations result in loss of enzyme function by preventing the biosynthesis of catalytically competent SI at the cell surface. Transcriptome analyses of RNA from CLL patients with SI loss-of-function mutations have uncovered gene expression patterns that depict ample metabolic reprogramming, pinpointing SI as a putative player in the cancer-associated metabolic switch. These results highlight SI as a relevant target for clinical evaluation in future CLL studies.