Despite the growing availability of multifunctional prosthetic hands, users' control and overall functional abilities with these hands remain limited. The combination of pattern recognition control ...and targeted muscle reinnervation (TMR) surgery, an innovative technique where amputated nerves are transferred to reinnervate new muscle targets in the residual limb, has been used to improve prosthesis control of individuals with more proximal upper limb amputations (i.e., shoulder disarticulation and transhumeral amputation).
The goal of this study was to determine if prosthesis hand grasp control improves following transradial TMR surgery.
Eight participants were trained to use a multi-articulating hand prosthesis under myoelectric pattern recognition control. All participated in home usage trials pre- and post-TMR surgery. Upper limb outcome measures were collected following each home trial.
Three outcome measures (Southampton Hand Assessment Procedure, Jebsen-Taylor Hand Function Test, and Box and Blocks Test) improved 9-12 months post-TMR surgery compared with pre-surgery measures. The Assessment of Capacity for Myoelectric Control and Activities Measure for Upper Limb Amputees outcome measures had no difference pre- and post-surgery. An offline electromyography analysis showed a decrease in grip classification error post-TMR surgery compared to pre-TMR surgery. Additionally, a majority of subjects noted qualitative improvements in their residual limb and phantom limb sensations post-TMR.
The potential for TMR surgery to result in more repeatable muscle contractions, possibly due to the reduction in pain levels and/or changes to phantom limb sensations, may increase functional use of many of the clinically available dexterous prosthetic hands.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Partitiviruses are segmented, multipartite double-stranded RNA (dsRNA) viruses that until recently were only known to infect fungi, plants, and protozoans. Metagenomic surveys have revealed that ...partitivirus-like sequences are also commonly associated with arthropods. One arthropod-associated partitivirus, galbut virus, is common in wild populations of
To begin to understand the processes that underlie this virus's high global prevalence, we established colonies of wild-caught infected flies. Infection remained at stably high levels over 3 years, with between 63 and 100% of individual flies infected. Galbut virus infects fly cells and replicates in tissues throughout infected adults, including reproductive tissues and the gut epithelium. We detected no evidence of horizontal transmission via ingestion, but vertical transmission from either infected females or infected males was ∼100% efficient. Vertical transmission of a related partitivirus, verdadero virus, that we discovered in a laboratory colony of
mosquitoes was similarly efficient. This suggests that efficient biparental vertical transmission may be a feature of at least a subset of insect-infecting partitiviruses. To study the impact of galbut virus infection free from the confounding effect of other viruses, we generated an inbred line of flies with galbut virus as the only detectable virus infection. We were able to transmit infection experimentally via microinjection of homogenate from these galbut-only flies. This sets the stage for experiments to understand the biological impact and possible utility of partitiviruses infecting model organisms and disease vectors.
Galbut virus is a recently discovered partitivirus that is extraordinarily common in wild populations of the model organism
Like for most viruses discovered through metagenomics, most of the basic biological questions about this virus remain unanswered. We found that galbut virus, along with a closely related partitivirus found in
mosquitoes, is transmitted from infected females or males to offspring with ∼100% efficiency and can be maintained in laboratory colonies over years. This efficient transmission mechanism likely underlies the successful spread of these viruses through insect populations. We created
lines that contained galbut virus as the only virus infection and showed that these flies can be used as a source for experimental infections. This provides insight into how arthropod-infecting partitiviruses may be maintained in nature and sets the stage for exploration of their biology and potential utility.
There is growing evidence from human and animal studies indicating an association between exposure to synthetic food dyes and adverse neurobehavioral outcomes in children. However, data gaps persist ...for potential mechanisms by which the synthetic food dyes could elicit neurobehavioral impacts. We developed an approach to evaluate seven US FDA-batch-certified food dyes using publicly available high-throughput screening (HTS) data from the US EPA’s Toxicity Forecaster to assess potential underlying molecular mechanisms that may be linked to neurological pathway perturbations. The dyes were screened through 270 assays identified based on whether they had a neurological-related gene target and/or were mapped to neurodevelopmental processes or neurobehavioral outcomes, and were conducted in brain tissue, targeted specific hormone receptors, or targeted oxidative stress and inflammation. Some results provided support for neurological impacts found in human and animal studies, while other results showed a lack of correlation with in vivo findings. The azo dyes had a range of activity in assays mapped to G-protein-coupled receptors and were active in assays targeting dopaminergic, serotonergic, and opioid receptors. Assays mapped to nuclear receptors (androgen, estrogen, and thyroid hormone) also exhibited activity with the food dyes. Other molecular targets included the aryl hydrocarbon receptor, acetylcholinesterase, and monoamine oxidase. The Toxicological Prioritization Index tool was used to visualize the results of the Novascreen assays. Our results highlight certain limitations of HTS assays but provide insight into potential underlying mechanisms of neurobehavioral effects observed in in vivo animal toxicology studies and human clinical studies.
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IJS, KILJ, NUK, PNG, UL, UM
The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the ...microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.
Immunotherapy with PD-1 or PD-L1 blockade fails to induce a response in about 80% of patients with unselected non-small cell lung cancer (NSCLC), and many of those who do initially respond then ...develop resistance to treatment. Agonists that target the shared interleukin-2 (IL-2) and IL-15Rβγ pathway have induced complete and durable responses in some cancers, but no studies have been done to assess the safety or efficacy of these agonists in combination with anti-PD-1 immunotherapy. We aimed to define the safety, tolerability, and activity of this drug combination in patients with NSCLC.
In this non-randomised, open-label, phase 1b trial, we enrolled patients (aged ≥18 years) with previously treated histologically or cytologically confirmed stage IIIB or IV NSCLC from three academic hospitals in the USA. Key eligibility criteria included measurable disease, eligibility to receive anti-PD-1 immunotherapy, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received the anti-PD-1 monoclonal antibody nivolumab intravenously at 3 mg/kg (then 240 mg when US Food and Drug Administration FDA-approved dosing changed) every 14 days (either as new treatment or continued treatment at the time of disease progression) and the IL-15 superagonist ALT-803 subcutaneously once per week on weeks 1–5 of four 6-week cycles for 6 months. ALT-803 was administered at one of four escalating dose concentrations: 6, 10, 15, or 20 μg/kg. The primary endpoint was to define safety and tolerability and to establish a recommended phase 2 dose of ALT-803 in combination with nivolumab. Analyses were per-protocol and included any patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT02523469; phase 2 enrolment of patients is ongoing.
Between Jan 18, 2016, and June 28, 2017, 23 patients were enrolled and 21 were treated at four dose levels of ALT-803 in combination with nivolumab. Two patients did not receive treatment because of the development of inter-current illness during enrolment, one patient due to leucopenia and one patient due to pulmonary dysfunction. No dose-limiting toxicities were recorded and the maximum tolerated dose was not reached. The most common adverse events were injection-site reactions (in 19 90% of 21 patients) and flu-like symptoms (15 71%). The most common grade 3 adverse events, occurring in two patients each, were lymphocytopenia and fatigue. A grade 3 myocardial infarction occurred in one patient. No grade 4 or 5 adverse events were recorded. The recommended phase 2 dose of ALT-803 is 20 μg/kg given once per week subcutaneously in combination with 240 mg intravenous nivolumab every 2 weeks.
ALT-803 in combination with nivolumab can be safely administered in an outpatient setting. The promising clinical activity observed with the addition of ALT-803 to the regimen of patients with PD-1 monoclonal antibody relapsed and refractory disease shows evidence of anti-tumour activity for a new class of agents in NSCLC.
Altor BioScience (a NantWorks company), National Institutes of Health, and Medical University of South Carolina Hollings Cancer Center.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the ...microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.
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