Use of acupuncture with acupressure in addition to standard-of-care cryotherapy to decrease chemotherapy-associated neuropathy in patients with gastrointestinal malignancies receiving oxaliplatin-based chemotherapy: Study protocol for a randomized, controlled pilot and feasibility study.

BACKGROUND: Oxaliplatin is a key chemotherapeutic agent in the treatment of local and metastatic gastrointestinal (GI) malignancies. Dose density and treatment adherence can be limited by chemotherapy-induced peripheral neuropathy (CIPN). Early research suggests CIPN incidence and severity may be mitigated by acupuncture, but rigorous data in GI oncology patients is limited. Here, we describe the protocol of a randomized, waitlist-controlled pilot study testing the use of preemptive of acupuncture plus acupressure to decrease CIPN and chemotherapy-related toxicities. METHODS: Patients with a GI malignancy (n = 56) with planned 5-fluorouracil (5-FU) and oxaliplatin IV (FOLFOX, FOLFIRINOX) every 2 weeks are being recruited. Additional concurrent anti-neoplastic agents may be used. Enrolled patients are randomized 1:1 to a 3-month intervention of Arm A: acupuncture with acupressure and standard-of-care treatment, or Arm B: standard-of-care alone. In Arm A, on days 1 and 3 of each chemotherapy cycle a standardized acupuncture protocol is administered and patients are taught self-acupressure to perform daily between chemotherapy treatments. Patients in both arms are given standard-of-care oral and peripheral (hands/feet) ice chip cryotherapy during oxaliplatin administration. CIPN and other symptoms are assessed at baseline, 6 weeks, and 3 months from registration. The primary endpoint is CIPN severity at 3 months (EORTC-CIPN 20). Additional endpoints evaluate CIPN incidence (CTCAE, Neuropen, tuning fork); incidence of pain, fatigue, nausea, oral dysesthesia, and anxiety; and feasibility (recruitment, retention, adherence, acceptability). If warranted, trial results will inform the design of a multi-center trial to expand testing of the intervention to a larger patient cohort.

Carbapenem-Resistant enterobacterales in individuals with and without health care risk factors -Emerging infections program, United States, 2012-2015.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are usually healthcare-associated but are also emerging in the community. METHODS: Active, population-based surveillance was conducted to identify case-patients with cultures positive for Enterobacterales not susceptible to a carbapenem (excluding ertapenem) and resistant to all third-generation cephalosporins tested at 8 US sites from January 2012 to December 2015. Medical records were used to classify cases as health care-associated, or as community-associated (CA) if a patient had no known health care risk factors and a culture was collected <3 days after hospital admission. Enterobacterales isolates from selected cases were submitted to CDC for whole genome sequencing. RESULTS: We identified 1499 CRE cases in 1194 case-patients; 149 cases (10%) in 139 case-patients were CA. The incidence of CRE cases per 100,000 population was 2.96 (95% CI: 2.81, 3.11) overall and 0.29 (95% CI: 0.25, 0.35) for CA-CRE. Most CA-CRE cases were in White persons (73%), females (84%) and identified from urine cultures (98%). Among the 12 sequenced CA-CRE isolates, 5 (42%) harbored a carbapenemase gene. CONCLUSIONS: Ten percent of CRE cases were CA; some isolates from CA-CRE cases harbored carbapenemase genes. Continued CRE surveillance in the community is critical to monitor emergence outside of traditional health care settings.

Learning and Transfer in Problem Solving Progressions.

Do individuals learn more effectively when given progressive or variable problem-solving experience, relative to consistent problem-solving experience? We investigated this question using a Rubik's Cube paradigm. Participants were randomly assigned to a progression-order condition, where they practiced solving three progressively more difficult Rubik's Cubes (i.e., 2 × 2 × 2 to 3 × 3 × 3 to 4 × 4 × 4), a variable-order condition, where they practiced solving three Rubik's Cubes of varying difficulty (e.g., 3 × 3 × 3 to 2 × 2 × 2 to 4 × 4 × 4), or a consistent-order condition, where they consistently practiced on three 5 × 5 × 5 Rubik's Cubes. All the participants then attempted a 5 × 5 × 5 Rubik's Cube test. We tested whether variable training is as effective as progressive training for near transfer of spatial skills and whether progressive training is superior to consistent training. We found no significant differences in performance across conditions. Participants' fluid reasoning predicted 5 × 5 × 5 Rubik's Cube test performance regardless of training condition.

Whole-Genome Sequencing Reveals Diversity of Carbapenem-Resistant Pseudomonas aeruginosa Collected through CDC's Emerging Infections Program, United States, 2016-2018.

The CDC's Emerging Infections Program (EIP) conducted population- and laboratory-based surveillance of US carbapenem-resistant Pseudomonas aeruginosa (CRPA) from 2016 through 2018. To characterize the pathotype, 1,019 isolates collected through this project underwent antimicrobial susceptibility testing and whole-genome sequencing. Sequenced genomes were classified using the seven-gene multilocus sequence typing (MLST) scheme and a core genome (cg)MLST scheme was used to determine phylogeny. Both chromosomal and horizontally transmitted mechanisms of carbapenem resistance were assessed. There were 336 sequence types (STs) among the 1,019 sequenced genomes, and the genomes varied by an average of 84.7% of the cgMLST alleles used. Mutations associated with dysfunction of the porin OprD were found in 888 (87.1%) of the genomes and were correlated with carbapenem resistance, and a machine learning model incorporating hundreds of genetic variations among the chromosomal mechanisms of resistance was able to classify resistant genomes. While only 7 (0.1%) isolates harbored carbapenemase genes, 66 (6.5%) had acquired non-carbapenemase ß-lactamase genes, and these were more likely to have OprD dysfunction and be resistant to all carbapenems tested. The genetic diversity demonstrates that the pathotype includes a variety of strains, and clones previously identified as high-risk make up only a minority of CRPA strains in the United States. The increased carbapenem resistance in isolates with acquired non-carbapenemase ß-lactamase genes suggests that horizontally transmitted mechanisms aside from carbapenemases themselves may be important drivers of the spread of carbapenem resistance in P. aeruginosa.

Molecular Epidemiology of Carbapenem-Resistant Acinetobacter baumannii in the United States, 2013-2017.

Healthcare-associated carbapenem-resistant Acinetobacter baumannii (CRAB) infections are a serious threat associated with global epidemic clones and a variety of carbapenemase gene classes. In this study, we describe the molecular epidemiology, including whole-genome sequencing analysis and antimicrobial susceptibility profiles of 92 selected, nonredundant CRAB collected through public health efforts in the United States from 2013 to 2017. Among the 92 isolates, the Oxford (OX) multilocus sequence typing scheme identified 30 sequence types (STs); the majority of isolates (n = 59, 64%) represented STs belonging to the international clonal complex 92 (CC92OX). Among these, ST208OX (n = 21) and ST281OX (n = 20) were the most common. All isolates carried an OXA-type carbapenemase gene, comprising 20 alleles. Ninety isolates (98%) encoded an intrinsic OXA-51-like enzyme; 67 (73%) harbored an additional acquired blaOXA gene, most commonly blaOXA-23 (n = 45; 49%). Compared with isolates harboring only intrinsic oxacillinase genes, acquired blaOXA gene presence was associated with higher prevalence of resistance and a higher median minimum inhibitory concentration to the carbapenem imipenem (64 µg/mL vs. 8 µg/mL), and antibiotics from other drug classes, including penicillin, aminoglycosides, cephalosporins, and polymyxins. These data illustrate the wide distribution of CC92OX and high prevalence of acquired blaOXA carbapenemase genes among CRAB in the United States.

Epidemiology of extended-spectrum ß-lactamase-producing Enterobacterales in five US sites participating in the Emerging Infections Program, 2017.

OBJECTIVE: The incidence of infections from extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales (ESBL-E) is increasing in the United States. We describe the epidemiology of ESBL-E at 5 Emerging Infections Program (EIP) sites. METHODS: During October-December 2017, we piloted active laboratory- and population-based (New York, New Mexico, Tennessee) or sentinel (Colorado, Georgia) ESBL-E surveillance. An incident case was the first isolation from normally sterile body sites or urine of Escherichia coli or Klebsiella pneumoniae/oxytoca resistant to ≥1 extended-spectrum cephalosporin and nonresistant to all carbapenems tested at a clinical laboratory from a surveillance area resident in a 30-day period. Demographic and clinical data were obtained from medical records. The Centers for Disease Control and Prevention (CDC) performed reference antimicrobial susceptibility testing and whole-genome sequencing on a convenience sample of case isolates. RESULTS: We identified 884 incident cases. The estimated annual incidence in sites conducting population-based surveillance was 199.7 per 100,000 population. Overall, 800 isolates (96%) were from urine, and 790 (89%) were E. coli. Also, 393 cases (47%) were community-associated. Among 136 isolates (15%) tested at the CDC, 122 (90%) met the surveillance definition phenotype; 114 (93%) of 122 were shown to be ESBL producers by clavulanate testing. In total, 111 (97%) of confirmed ESBL producers harbored a blaCTX-M gene. Among ESBL-producing E. coli isolates, 52 (54%) were ST131; 44% of these cases were community associated. CONCLUSIONS: The burden of ESBL-E was high across surveillance sites, with nearly half of cases acquired in the community. EIP has implemented ongoing ESBL-E surveillance to inform prevention efforts, particularly in the community and to watch for the emergence of new ESBL-E strains.

Molecular Characterization of Carbapenem-Resistant Enterobacterales Collected in the United States.

Carbapenem-resistant Enterobacterales (CRE) are a growing public health concern due to resistance to multiple antibiotics and potential to cause health care-associated infections with high mortality. Carbapenemase-producing CRE are of particular concern given that carbapenemase-encoding genes often are located on mobile genetic elements that may spread between different organisms and species. In this study, we performed phenotypic and genotypic characterization of CRE collected at eight U.S. sites participating in active population- and laboratory-based surveillance of carbapenem-resistant organisms. Among 421 CRE tested, the majority were isolated from urine (n = 349, 83%). Klebsiella pneumoniae was the most common organism (n = 265, 63%), followed by Enterobacter cloacae complex (n = 77, 18%) and Escherichia coli (n = 50, 12%). Of 419 isolates analyzed by whole genome sequencing, 307 (73%) harbored a carbapenemase gene; variants of blaKPC predominated (n = 299, 97%). The occurrence of carbapenemase-producing K. pneumoniae, E. cloacae complex, and E. coli varied by region; the predominant sequence type within each genus was ST258, ST171, and ST131, respectively. None of the carbapenemase-producing CRE isolates displayed resistance to all antimicrobials tested; susceptibility to amikacin and tigecycline was generally retained.

Monitoring Laboratory Occupational Exposures to Burkholderia pseudomallei.

Background: Burkholderia pseudomallei is a Tier 1 overlap select agent and subject to the select agent regulations (42 CFR §73 and 9 CFR §121). It is a gram-negative, motile, soil saprophyte, and the etiologic agent of melioidosis. B. pseudomallei infection can produce systemic illness and can be fatal in the absence of appropriate treatment. Laboratory exposures involving this organism may occur when appropriate containment measures are not employed. Current disease treatment inadequacies and the risk factors associated with melioidosis make this an agent of primary concern in research, commercial, and clinical laboratory environments. Results: This study presents data reported to Centers for Disease Control and Prevention (CDC), Division of Select Agents and Toxins for releases involving B. pseudomallei in 2017-2019 that occurred in Biosafety Level (BSL)-2 and BSL-3 laboratories. Fifty-one Animal and Plant Health Inspection Service (APHIS)/CDC Form 3 release reports led to the medical surveillance of 275 individuals. Entities offered post-exposure prophylaxis to ∼76% of the individuals impacted in the presented events. Summary: Laboratory safety can be improved by implementing appropriate safety precautions to minimize exposures. Most of the incidents discussed in this evidence-based report occurred during work conducted in the absence of primary containment. None of the releases resulted in illness, death, or transmission to or among workers, nor was there transmission outside of a laboratory into the surrounding environment or community. Effective risk assessment and management strategies coupled with standard and special microbiological policies and procedures can result in reduced exposures and improved safety at facilities.

Multiview confocal super-resolution microscopy.

Confocal microscopy1 remains a major workhorse in biomedical optical microscopy owing to its reliability and flexibility in imaging various samples, but suffers from substantial point spread function anisotropy, diffraction-limited resolution, depth-dependent degradation in scattering samples and volumetric bleaching2. Here we address these problems, enhancing confocal microscopy performance from the sub-micrometre to millimetre spatial scale and the millisecond to hour temporal scale, improving both lateral and axial resolution more than twofold while simultaneously reducing phototoxicity. We achieve these gains using an integrated, four-pronged approach: (1) developing compact line scanners that enable sensitive, rapid, diffraction-limited imaging over large areas; (2) combining line-scanning with multiview imaging, developing reconstruction algorithms that improve resolution isotropy and recover signal otherwise lost to scattering; (3) adapting techniques from structured illumination microscopy, achieving super-resolution imaging in densely labelled, thick samples; (4) synergizing deep learning with these advances, further improving imaging speed, resolution and duration. We demonstrate these capabilities on more than 20 distinct fixed and live samples, including protein distributions in single cells; nuclei and developing neurons in Caenorhabditis elegans embryos, larvae and adults; myoblasts in imaginal disks of Drosophila wings; and mouse renal, oesophageal, cardiac and brain tissues.

Pregnancy, Birth, Infant, and Early Childhood Neurodevelopmental Outcomes among a Cohort of Women with Symptoms of Zika Virus Disease during Pregnancy in Three Surveillance Sites, Project Vigilancia de Embarazadas con Zika (VEZ), Colombia, 2016-2018.

Project Vigilancia de Embarazadas con Zika (VEZ), an intensified surveillance of pregnant women with symptoms of the Zika virus disease (ZVD) in Colombia, aimed to evaluate the relationship between symptoms of ZVD during pregnancy and adverse pregnancy, birth, and infant outcomes and early childhood neurodevelopmental outcomes. During May-November 2016, pregnant women in three Colombian cities who were reported with symptoms of ZVD to the national surveillance system, or with symptoms of ZVD visiting participating clinics, were enrolled in Project VEZ. Data from maternal and pediatric (up to two years of age) medical records were abstracted. Available maternal specimens were tested for the presence of the Zika virus ribonucleic acid and/or anti-Zika virus immunoglobulin antibodies. Of 1213 enrolled pregnant women with symptoms of ZVD, 1180 had a known pregnancy outcome. Results of the Zika virus laboratory testing were available for 569 (48.2%) pregnancies with a known pregnancy outcome though testing timing varied and was often distal to the timing of symptoms; 254 (21.5% of the whole cohort; 44.6% of those with testing results) were confirmed or presumptive positive for the Zika virus infection. Of pregnancies with a known outcome, 50 (4.2%) fetuses/infants had Zika-associated brain or eye defects, which included microcephaly at birth. Early childhood adverse neurodevelopmental outcomes were more common among those with Zika-associated birth defects than among those without and more common among those with laboratory evidence of a Zika virus infection compared with the full cohort. The proportion of fetuses/infants with any Zika-associated brain or eye defect was consistent with the proportion seen in other studies. Enhancements to Colombia's existing national surveillance enabled the assessment of adverse outcomes associated with ZVD in pregnancy.

Detection of CTX-M-27 ß-Lactamase Genes on Two Distinct Plasmid Types in ST38 Escherichia coli from Three U.S. States.

Infections caused by extended-spectrum-ß-lactamase (ESBL)-producing Escherichia coli are a significant cause of morbidity and health care costs. Globally, the prevailing clonal type is ST131 in association with the blaCTX-M-15 ß-lactamase gene. However, other ESBLs, such as blaCTX-M-14 and blaCTX-M-27, can also be prevalent in some regions. We identified ST38 ESBL-producing E. coli from different regions in the United States which carry blaCTX-M-27 embedded on two distinct plasmid types, suggesting the potential emergence of new ESBL lineages.

Colonization of carbapenem-resistant Klebsiella pneumoniae in a sink-drain model biofilm system.

BACKGROUND: Sink drains in healthcare facilities may provide an environment for antimicrobial-resistant microorganisms, including carbapenemase-producing Klebsiella pneumoniae (CPKP). METHODS: We investigated the colonization of a biofilm consortia by CPKP in a model system simulating a sink-drain P-trap. Centers for Disease Control (CDC) biofilm reactors (CBRs) were inoculated with microbial consortia originally recovered from 2 P-traps collected from separate patient rooms (designated rooms A and B) in a hospital. Biofilms were grown on stainless steel (SS) or polyvinyl chloride (PVC) coupons in autoclaved municipal drinking water (ATW) for 7 or 28 days. RESULTS: Microbial communities in model systems (designated CBR-A or CBR-B) were less diverse than communities in respective P-traps A and B, and they were primarily composed of ß and γ Proteobacteria, as determined using 16S rRNA community analysis. Following biofilm development CBRs were inoculated with either K. pneumoniae ST45 (ie, strain CAV1016) or K. pneumoniae ST258 KPC+ (ie, strain 258), and samples were collected over 21 days. Under most conditions tested (CBR-A: SS, 7-day biofilm; CBR-A: PVC, 28-day biofilm; CBR-B: SS, 7-day and 28-day biofilm; CBR-B: PVC, 28-day biofilm) significantly higher numbers of CAV1016 were observed compared to 258. CAV1016 showed no significant difference in quantity or persistence based on biofilm age (7 days vs 28 days) or substratum type (SS vs PVC). However, counts of 258 were significantly higher on 28-day biofilms and on SS. CONCLUSIONS: These results suggest that CPKP persistence in P-trap biofilms may be strain specific or may be related to the type of P-trap material or age of the biofilm.

Development and Application of a Core Genome Multilocus Sequence Typing Scheme for the Health Care-Associated Pathogen Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic human pathogen that frequently causes health care-associated infections (HAIs). Due to its metabolic diversity and ability to form biofilms, this Gram-negative nonfermenting bacterium can persist in the health care environment, which can lead to prolonged HAI outbreaks. We describe the creation of a core genome multilocus sequence typing (cgMLST) scheme to provide a stable platform for the rapid comparison of P. aeruginosa isolates using whole-genome sequencing (WGS) data. We used a diverse set of 58 complete P. aeruginosa genomes to curate a set of 4,440 core genes found in each isolate, representing ∼64% of the average genome size. We then expanded the alleles for each gene using 1,991 contig-level genome sequences. The scheme was used to analyze genomes from four historical HAI outbreaks to compare the phylogenies generated using cgMLST to those of other means (traditional MLST, pulsed-field gel electrophoresis [PFGE], and single-nucleotide variant [SNV] analysis). The cgMLST scheme provides sufficient resolution for analyzing individual outbreaks, as well as the stability for comparisons across a variety of isolates encountered in surveillance studies, making it a valuable tool for the rapid analysis of P. aeruginosa genomes.

Multicenter Outbreak of Gram-Negative Bloodstream Infections in Hemodialysis Patients.

RATIONALE & OBJECTIVE: Contaminated water and other fluids are increasingly recognized to be associated with health care-associated infections. We investigated an outbreak of Gram-negative bloodstream infections at 3 outpatient hemodialysis facilities. STUDY DESIGN: Matched case-control investigations. SETTING & PARTICIPANTS: Patients who received hemodialysis at Facility A, B, or C from July 2015 to November 2016. EXPOSURES: Infection control practices, sources of water, dialyzer reuse, injection medication handling, dialysis circuit priming, water and dialysate test findings, environmental reservoirs such as wall boxes, vascular access care practices, pulsed-field gel electrophoresis, and whole-genome sequencing of bacterial isolates. OUTCOMES: Cases were defined by a positive blood culture for any Gram-negative bacteria drawn July 1, 2015 to November 30, 2016 from a patient who had received hemodialysis at Facility A, B, or C. ANALYTICAL APPROACH: Exposures in cases and controls were compared using matched univariate conditional logistic regression. RESULTS: 58 cases of Gram-negative bloodstream infection occurred; 48 (83%) required hospitalization. The predominant organisms were Serratia marcescens (n=21) and Pseudomonas aeruginosa (n=12). Compared with controls, cases had higher odds of using a central venous catheter for dialysis (matched odds ratio, 54.32; lower bound of the 95% CI, 12.19). Facility staff reported pooling and regurgitation of waste fluid at recessed wall boxes that house connections for dialysate components and the effluent drain within dialysis treatment stations. Environmental samples yielded S marcescens and P aeruginosa from wall boxes. S marcescens isolated from wall boxes and case-patients from the same facilities were closely related by pulsed-field gel electrophoresis and whole-genome sequencing. We identified opportunities for health care workers' hands to contaminate central venous catheters with contaminated fluid from the wall boxes. LIMITATIONS: Limited patient isolates for testing, on-site investigation occurred after peak of infections. CONCLUSIONS: This large outbreak was linked to wall boxes, a previously undescribed source of contaminated fluid and biofilms in the immediate patient care environment.

Multi-immersion open-top light-sheet microscope for high-throughput imaging of cleared tissues.

Recent advances in optical clearing and light-sheet microscopy have provided unprecedented access to structural and molecular information from intact tissues. However, current light-sheet microscopes have imposed constraints on the size, shape, number of specimens, and compatibility with various clearing protocols. Here we present a multi-immersion open-top light-sheet microscope that enables simple mounting of multiple specimens processed with a variety of clearing protocols, which will facilitate wide adoption by preclinical researchers and clinical laboratories. In particular, the open-top geometry provides unsurpassed versatility to interface with a wide range of accessory technologies in the future.

Development and Validation of a Clinical Laboratory Improvement Amendments-Compliant Multiplex Real-Time PCR Assay for Detection of mcr Genes.

Increased use of colistin in both human and veterinary medicine has led to the emergence of plasmid-mediated colistin resistance (mcr genes). In this study, we report the development of a real-time PCR assay using TaqMan probe-based chemistry for detection of mcr genes from bacterial isolates. Positive control isolates harboring mcr-1 and mcr-2 yielded exponential amplification curves with the assay, and the amplification efficiency was 98% and 96% for mcr-1 and mcr-2, respectively. Each target gene could be reproducibly detected from a sample containing 103 cfu/mL of mcr-harboring bacteria, and there was no cross-reactivity with DNA extracted from several multidrug-resistant bacteria harboring other resistance genes, but lacking mcr genes. Both sensitivity and specificity of the mcr real-time PCR assay were 100% in a method validation performed with a set of 25 previously well-characterized bacterial isolates containing mcr-positive and -negative bacteria. This newly developed assay is a rapid and sensitive tool for detecting emerging mcr genes in cultured bacterial isolates. The assay was successfully validated according to quality standards of the Clinical Laboratory Improvement Amendments (CLIA).

Scalable Nanogap Sensors for Non-Redox Enzyme Assays.

Clinical diagnostic assays that monitor redox enzyme activity are widely used in small, low-cost readout devices for point-of-care monitoring (e.g., a glucometer); however, monitoring non-redox enzymes in real-time using compact electronic devices remains a challenge. We address this problem by using a highly scalable nanogap sensor array to observe electrochemical signals generated by a model non-redox enzyme system, the DNA polymerase-catalyzed incorporation of four modified, redox-tagged nucleotides. Using deoxynucleoside triphosphates (dNTPs) tagged with para-aminophenyl monophosphate (pAPP) to form pAP-deoxyribonucleoside tetra-phosphates (AP-dN4Ps), incorporation of the nucleotide analogs by DNA polymerase results in the release of redox inactive pAP-triphosphates (pAPP3) that are converted to redox active small molecules para-aminophenol (pAP) in the presence of phosphatase. In this work, cyclic enzymatic reactions that generated many copies of pAP at each base incorporation site of a DNA template in combination with the highly confined nature of the planar nanogap transducers ( z = 50 nm) produced electrochemical signals that were amplified up to 100,000×. We observed that the maximum signal level and amplification level were dependent on a combination of factors including the base structure of the incorporated nucleotide analogs, nanogap electrode materials, and electrode surface coating. In addition, electrochemical signal amplification by redox cycling in the nanogap is independent of the in-plane geometry of the transducer, thus allowing the nanogap sensors to be highly scalable. Finally, when the DNA template concentration was constrained, the DNA polymerase assay exhibited different zero-order reaction kinetics for each type of base incorporation reaction, resolving the closely related nucleotide analogs.

Visualizing Calcium Flux in Freely Moving Nematode Embryos.

The lack of physiological recordings from Caenorhabditis elegans embryos stands in stark contrast to the comprehensive anatomical and gene expression datasets already available. Using light-sheet fluorescence microscopy to address the challenges associated with functional imaging at this developmental stage, we recorded calcium dynamics in muscles and neurons and developed analysis strategies to relate activity and movement. In muscles, we found that the initiation of twitching was associated with a spreading calcium wave in a dorsal muscle bundle. Correlated activity in muscle bundles was linked with early twitching and eventual coordinated movement. To identify neuronal correlates of behavior, we monitored brainwide activity with subcellular resolution and identified a particularly active cell associated with muscle contractions. Finally, imaging neurons of a well-defined adult motor circuit, we found that reversals in the eggshell correlated with calcium transients in AVA interneurons.

Training response to high-intensity interval training in a 42-year-old man with chronic spinal cord injury.

OBJECTIVE: To review the outcome of 12 weeks of periodized, high-intensity interval training (HIT) in a man with chronic traumatic spinal cord injury (SCI). METHODS: A 42-year-old man (180 cm tall, 68.4 kg and 32.0% Fat) with a C8/T1 motor complete SCI took part in 12 weeks of 3 days per week arm crank ergometry (ACE) interval training. Training consisted of a combination of HIT that included three times 5  min at ∼70% Peak Power (WPeak) and 5  min recovery (HIT5); four times 2.5  min at ∼85% WPeak and 5  min recovery (HIT2.5); ten times 1  min at ∼110% WPeak and 2  min recovery (HIT1). Heart rate (HR) zones were set as <75% HRPeak (Z1), 75-89% (Z2), and 90+% (Z3) and used to monitor overall training efficacy. RESULTS: Thirty-six sessions that included 8 HIT5, 10 HIT2.5, and 5 HIT1 sessions were completed. WPeak and VO2 Peak improved about 45% and 52%, respectively, by week 6, without further improvement at week 12, HR TRIMP scores and power in training sessions trended upward over the 12-week program. CONCLUSIONS: Twelve weeks of HIT resulted in a large increase in peak aerobic power, as well as submaximal endurance performance in our participant. The early plateau in maximal testing supports the use of submaximal training assessment important in the long-term training monitoring for SCI.