Inter-species gene flow drives ongoing evolution of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis.

Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species, Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE and S. pyogenes. More than 75% of core genes are shared between the two species with one third demonstrating evidence of cross-species recombination. Twenty-five percent of mobile genetic element (MGE) clusters and 16 of 55 SDSE MGE insertion regions were shared across species. Assessing potential cross-protection from leading S. pyogenes vaccine candidates on SDSE, 12/34 preclinical vaccine antigen genes were shown to be present in >99% of isolates of both species. Relevant to possible vaccine evasion, six vaccine candidate genes demonstrated evidence of inter-species recombination. These findings demonstrate previously unappreciated levels of genomic overlap between these closely related pathogens with implications for streptococcal pathobiology, disease surveillance and prevention.

Discovery of ginisortamab, a potent and novel anti-gremlin-1 antibody in clinical development for the treatment of cancer.

Gremlin-1, a high-affinity antagonist of bone morphogenetic proteins (BMP)-2, -4, and -7, is implicated in tumor initiation and progression. Increased gremlin-1 expression, and therefore suppressed BMP signaling, correlates with poor prognosis in a range of cancer types. A lack of published work using therapeutic modalities has precluded the testing of the hypothesis that blocking the gremlin-1/BMP interaction will provide benefits to patients. To address this shortfall, we developed ginisortamab (UCB6114), a first-in-class clinical anti-human gremlin-1 antibody, currently in clinical development for the treatment of cancer, along with its murine analog antibody Ab7326 mouse immunoglobulin G1 (mIgG1). Surface plasmon resonance assays revealed that ginisortamab and Ab7326 mIgG1 had similar affinities for human and mouse gremlin-1, with mean equilibrium dissociation constants of 87 pM and 61 pM, respectively. The gremlin-1/Ab7326 antigen-binding fragment (Fab) crystal structure revealed a gremlin-1 dimer with a Fab molecule bound to each monomer that blocked BMP binding. In cell culture experiments, ginisortamab fully blocked the activity of recombinant human gremlin-1, and restored BMP signaling pathways in human colorectal cancer (CRC) cell lines. Furthermore, in a human CRC - fibroblast co-culture system where gremlin-1 is produced by the fibroblasts, ginisortamab restored BMP signaling in both the CRC cells and fibroblasts, demonstrating its activity in a relevant human tumor microenvironment model. The safety and efficacy of ginisortamab are currently being evaluated in a Phase 1/2 clinical trial in patients with advanced solid tumors (NCT04393298).

Development and pre-clinical evaluation of a Zika virus diagnostic for low resource settings.

Introduction: Zika virus (ZIKV) is a re-emerging flavivirus that poses a significant public health threat. ZIKV exhibits a wide array of non-vector borne human transmission routes, such as sexual transmission, transplacental transmission and blood transfusion. Detection and surveillance of ZIKV is considered paramount in prevention of major outbreaks. With the majority of cases reported in low-resource locations, simple, low-cost detection methods are considered highly desirable. Materials and Methods: Here we have developed a sensitive and specific ZIKV diagnostic using reverse transcription recombinase-aided amplification (RT-RAA) coupled with lateral flow detection (LFD) targeting a highly conserved region of the ZIKV NS1 gene. Results: We show our rapid, isothermal-ZIKV-diagnostic (Iso-ZIKV-Dx) can detect 500 copies of synthetic ZIKV RNA/µL in under 30 min at a constant 39°C. Using simulated urine samples, we observed that Iso-ZIKV-Dx also detects as low as 34.28 RNA copies/reaction of ZIKV (MR766 strain). Specificity testing confirmed that our test does not detect any co-circulating flaviviruses (dengue, West Nile, Japanese encephalitis, Murray Valley encephalitis and yellow fever viruses) or chikungunya virus. Sample processing results show complete inactivation of ZIKV (MR766 strain) in 5 min at room temperature using our novel viral RNA sample preparation reagent. Furthermore, lateral flow strips testing demonstrates positive diagnoses in as little as 5 min in running buffer. Discussion: Contrary to conventional RT-qPCR, our Iso-ZIKV-Dx does not require expensive machinery, specialised laboratory settings or extensively trained personnel. Pre-clinical evaluation demonstrates that our test exhibits robust, in-field capabilities without compromising sensitivity or specificity. When compared to the gold-standard RT-qPCR, our Iso-ZIKV-Dx test offers an array of applications that extend beyond diagnostics alone, including potential for surveillance and monitoring of ZIKV vector competency.

Classifying Intensity Domains From Arm Cycle Ergometry Differs Versus Leg Cycling Ergometry.

ABSTRACT: Astorino, TA, Robson, T, and McMillan, DW. Classifying intensity domains from arm cycle ergometry differs versus leg cycling ergometry. J Strength Cond Res 37(11): 2192-2199, 2023-This study compared the distribution of exercise intensity domains in response to progressive leg cycle ergometry (LCE) and arm cycle ergometry (ACE). Seventeen active men and women (age and body fat = 26 ± 7 years and 18 ± 3%) initially performed graded exercise on each modality to assess maximal oxygen uptake (V̇o2max) and peak power output (PPO). Using a randomized crossover design, they subsequently performed moderate intensity continuous exercise consisting of three 15-minute bouts at 20, 40, and 60% PPO on each modality. Gas exchange data (V̇o2, V̇co2, and VE), respiratory exchange ratio, heart rate (HR), blood lactate concentration (BLa), and perceptual responses were acquired. Only 2 subjects were classified in the same intensity domains across modalities, with LCE eliciting more subjects exercising at "vigorous" and "near-maximal" intensities than ACE. Time spent above 70 (22 ± 7 vs. 15 ± 8 minutes, d = 1.03) and 80 %HRmax (15 ± 6 vs. 9 ± 6 minutes, d = 1.04) was significantly greater with LCE vs. ACE. Compared with ACE, LCE revealed significantly higher (p < 0.05) peak (94 ± 6 vs. 88 ± 9 %HRmax, d = 0.81) and mean HR (73 ± 6 vs. 66 ± 6 %HRmax, d = 1.20), V̇o2 (54 ± 5 vs. 50 ± 7 %V̇o2max, d = 0.68), and BLa (5.5 ± 2.0 vs. 4.7 ± 1.5 mM, d = 0.48). The results exhibit that progressive leg cycling at identical intensities elicits a greater cardiometabolic stimulus than ACE.

Persons With Spinal Cord Injury Report Peripherally Dominant Serotonin-Like Syndrome After Use of Serotonergic Psychedelics.

Psychedelic-assisted therapy (PAT) may treat various mental health conditions. Despite its promising therapeutic signal across mental health outcomes, less attention is paid on its potential to provide therapeutic benefits across complex medical situations within rehabilitation medicine. Persons with spinal cord injury (SCI) have a high prevalence of treatment-resistant mental health comorbidities that compound the extent of their physical disability. Reports from online discussion forums suggest that those living with SCI are using psychedelics, though the motivation for their use is unknown. These anecdotal reports describe a consistent phenomenon of neuromuscular and autonomic hypersensitivity to classical serotonergic psychedelics, such as psilocybin and lysergic acid diethylamide (LSD). Persons describe intense muscle spasms, sweating, and tremors, with an eventual return to baseline and no reports of worsening of their baseline neurological deficits. The discomfort experienced interferes with the subjective beneficial effects self-reported. This phenomenon has not been described previously in the academic literature. We aim to provide a descriptive review and explanatory theoretical framework hypothesizing this phenomenon as a peripherally dominant serotonin syndrome-like clinical picture-that should be considered as such when persons with SCI are exposed to classical psychedelics. Raising awareness of this syndrome may help our mechanistic understanding of serotonergic psychedelics and stimulate development of treatment protocols permitting persons with SCI to safely tolerate their adverse effects. As PAT transitions from research trials into accepted clinical and decriminalized use, efforts must be made from a harm reduction perspective to understand these adverse events, while also serving as an informed consent process aid if such therapeutic approaches are to be considered for use in persons living with SCI.

Association between parenteral nutrition-containing intravenous lipid emulsion and bloodstream infections in patients with single-lumen central venous access: A secondary analysis of a randomized trial.

BACKGROUND: Distinguishing primary bloodstream infections (BSIs) related to central venous access devices (CVADs) from those that occur through other mechanisms, such as a damaged mucosal barrier, is difficult. METHODS: Secondary analysis was conducted on data from patients with CVADs that were collected for a large, randomized trial. Patients were divided into two groups: those who received parenteral nutrition (PN)-containing intravenous lipid emulsion (ILE) and those who did not have PN-containing ILE. This study investigated the influence of PN-containing ILE (ILE PN) on primary BSIs in patients with a CVAD. RESULTS: Of the 807 patients, 180 (22%) received ILE PN. Most (627/807; 73%) were recruited from the hematology and hematopoietic stem cell transplant unit, followed by surgical (90/807; 11%), trauma and burns (61/807; 8%), medical (44/807; 5%), and oncology (23/807; 3%). When primary BSI was differentiated as a central line-associated BSI (CLABSI) or mucosal barrier injury laboratory-confirmed BSI (MBI-LCBI), the incidence of CLABSI was similar in the ILE PN and non-ILE PN groups (15/180 [8%] vs 57/627 [9%]; P = 0.88) and the incidence of MBI-LCBI was significantly different between groups (31/180 [17%] ILE PN vs 41/627 [7%] non-ILE PN; P < 0.01). CONCLUSION: Our data indicate that twice as many primary BSIs in ILE PN patients are due to MBIs than CVADs. It is important to consider the MBI-LCBI classification, as some CLABSI prevention efforts aimed at CVADs for the ILE PN population may be better directed to gastrointestinal tract protection interventions.

The Physiology of Neurogenic Obesity: Lessons from Spinal Cord Injury Research.

BACKGROUND: A spinal cord injury (SCI) from trauma or disease impairs sensorimotor pathways in somatic and autonomic divisions of the nervous system, affecting multiple body systems. Improved medical practices have increased survivability and life expectancy after SCI, allowing for the development of extensive metabolic comorbidities and profound changes in body composition that culminate in prevalent obesity. SUMMARY: Obesity is the most common cardiometabolic component risk in people living with SCI, with a diagnostic body mass index cutoff of 22 kg/m2 to account for a phenotype of high adiposity and low lean mass. The metameric organization of specific divisions of the nervous system results in level-dependent pathology, with resulting sympathetic decentralization altering physiological functions such as lipolysis, hepatic lipoprotein metabolism, dietary fat absorption, and neuroendocrine signaling. In this manner, SCI provides a unique opportunity to study in vivo the "neurogenic" components of certain pathologies that otherwise are not readily observable in other populations. We discuss the unique physiology of neurogenic obesity after SCI, including the altered functions mentioned above as well as structural changes such as reduced skeletal muscle and bone mass and increased lipid deposition in the adipose tissue, skeletal muscle, bone marrow, and liver. KEY MESSAGE: The study of neurogenic obesity after SCI gives us a unique neurological perspective on the physiology of obesity. The lessons learned from this field can guide future research and advancements to inform the study of obesity in persons with and without SCI.

Importance of timing optimization for closed-loop applications of vagus nerve stimulation.

In recent decades, vagus nerve stimulation (VNS) therapy has become widely used for clinical applications including epilepsy, depression, and enhancing the effects of rehabilitation. However, several questions remain regarding optimization of this therapy to maximize clinical outcomes. Although stimulation parameters such as pulse width, amplitude, and frequency are well studied, the timing of stimulation delivery both acutely (with respect to disease events) and chronically (over the timeline of a disease's progression) has generally received less attention. Leveraging such information would provide a framework for the implementation of next generation closed-loop VNS therapies. In this mini-review, we summarize a number of VNS therapies and discuss (1) general timing considerations for these applications and (2) open questions that could lead to further therapy optimization.

Student engagement and comprehension using tactile and virtual learning.

PURPOSE/OBJECTIVES: Dental students' levels of engagement and comprehension were assessed using tactile learning (with physical teeth) versus virtual learning (using computer images) in a dental histology course. Differences in engagement and comprehension by learning preferences were also examined. METHODS: One hundred first-year dental students were randomly divided into twenty teams of five students. Conditions were counterbalanced such that half the students were given physical tooth models (Group A) while the other half were given access to virtual images of tooth models (Group B) during the first session. Conditions were switched for a second session. Both groups completed the same learning exercise and formative assessment (quiz) after each session. A survey assessed students' learning preferences and attitudes. RESULTS: There were no differences by group assignment in both formative assessment scores and learning preferences (p > 0.10). For all students, comprehension of material was significantly higher in the tactile condition (with physical teeth) compared to the virtual experience (p = 0.01), but there was no difference in engagement between conditions (p = 0.35). Students who preferred learning with physical tooth models had higher engagement when using the physical tooth models compared to those who preferred virtual tooth models (p = 0.04), and significantly more positive attitudes toward physical tooth models (p's < 0.0001). CONCLUSION: Results suggest that for dental students, learning activities involving handling physical teeth may produce greater comprehension than viewing virtual images of teeth on a screen. More research is needed to determine the circumstances when virtual images can be substituted for physical models or be a beneficial adjunct method.

Rapid Diagnostic Tests for the Detection of the Four Dengue Virus Serotypes in Clinically Relevant Matrices.

The efficient and accurate diagnosis of dengue, a major mosquito-borne disease, is of primary importance for clinical care, surveillance, and outbreak control. The identification of specific dengue virus serotype 1 (DENV-1) to DENV-4 can help in understanding the transmission dynamics and spread of dengue disease. The four rapid low-resource serotype-specific dengue tests use a simple sample preparation reagent followed by reverse transcription-isothermal recombinase polymerase amplification (RT-RPA) combined with lateral flow detection (LFD) technology. Results are obtained directly from clinical sample matrices in 35 min, requiring only a heating block and pipettes for liquid handling. In addition, we demonstrate that the rapid sample preparation step inactivates DENV, improving laboratory safety. Human plasma and serum were spiked with DENV, and DENV was detected with analytical sensitivities of 333 to 22,500 median tissue culture infectious doses (TCID50)/mL. The analytical sensitivities in blood were 94,000 to 333,000 TCID50/mL. Analytical specificity testing confirmed that each test could detect multiple serotype-specific strains but did not respond to strains of other serotypes, closely related flaviviruses, or chikungunya virus. Clinical testing on 80 human serum samples demonstrated test specificities of between 94 and 100%, with a DENV-2 test sensitivity of 100%, detecting down to 0.004 PFU/µL, similar to the sensitivity of the PCR test; the other DENV tests detected down to 0.03 to 10.9 PFU/µL. Collectively, our data suggest that some of our rapid dengue serotyping tests provide a potential alternative to conventional labor-intensive RT-quantitative PCR (RT-qPCR) detection, which requires expensive thermal cycling instrumentation, technical expertise, and prolonged testing times. Our tests provide performance and speed without compromising specificity in human plasma and serum and could become promising tools for the detection of high DENV loads in resource-limited settings. IMPORTANCE The efficient and accurate diagnosis of dengue, a major mosquito-borne disease, is of primary importance for clinical care, surveillance, and outbreak control. This study describes the evaluation of four rapid low-resource serotype-specific dengue tests for the detection of specific DENV serotypes in clinical sample matrices. The tests use a simple sample preparation reagent followed by reverse transcription-isothermal recombinase polymerase amplification (RT-RPA) combined with lateral flow detection (LFD) technology. These tests have several advantages compared to RT-qPCR detection, such as a simple workflow, rapid sample processing and turnaround times (35 min from sample preparation to detection), minimal equipment needs, and improved laboratory safety through the inactivation of the virus during the sample preparation step. The low-resource formats of these rapid dengue serotyping tests have the potential to support effective dengue disease surveillance and enhance the diagnostic testing capacity in resource-limited countries with both endemic dengue and intense coronavirus disease 2019 (COVID-19) transmission.

Complex network analysis of volatility spillovers between global financial indicators and G20 stock markets.

This paper analyses the dynamic transmission mechanism of volatility spillovers between key global financial indicators and G20 stock markets. To examine volatility spillover relations, we combine a bivariate GARCH-BEKK model with complex network theory. Specifically, we construct a volatility network of international financial markets utilising the spatial connectedness of spillovers (consisting of nodes and edges). The findings show that spillover relations between global variables and G20 markets vary significantly across five identified sub-periods. Notably, networks are much denser in crisis periods compared to non-crisis periods. In comparing two crisis periods, Global Financial Crisis (2008) and COVID-19 Crisis (2020) periods, the network statistics suggest that volatility spillovers in the latter period are more transitive and intense than the former. This suggests that financial volatility spreads more rapidly and directly through key financial indicators to the G20 stock markets. For example, oil and bonds are the largest volatility senders, while the markets of Saudi Arabia, Russia, South Africa, and Brazil are the main volatility receivers. In the former crisis, the source of financial volatility concentrates primarily in the USA, Australia, Canada, and Saudi Arabia, which are the largest volatility senders and receivers. China emerges as generally the least sensitive market to external volatility.

Modulation of PTH1R signaling by an extracellular binding antibody.

Parathyroid hormone receptor 1 (PTH1R) is a class B G-protein coupled receptor with key roles in bone development. The receptor signals through both the Gs and Gq G-proteins as well as through ß-arrestin in a G-protein independent manner. Current treatments for bone disorders, such as osteoporosis, target the PTH1R but are suboptimal in their efficacy. Monoclonal antibodies represent a major growth area in therapeutics as a result of their superior specificity and long serum half-life. Here, we discovered antibodies against the extracellular domain (ECD) of PTH1R from a phage display library. One of these antibodies, ECD-ScFvhFc, binds PTH1R with high affinity and although it has little or no effect on G-protein dependent receptor signaling, it does reduce PTH1R mediated ß-arrestin signaling. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) demonstrated that the ECD-ScFvhFc binding site overlapped partially with that of the cognate ligand, PTH. The results of this study demonstrate the suitability of PTH1R as a target for therapeutic antibody development.

Use of low-frequency contact ultrasonic debridement with and without polyhexamethylene biguanide in hard-to-heal leg ulcers: an RCT.

OBJECTIVE: The primary aim of this research was to investigate the combination effect of polyhexamethylene biguanide (PHMB) and low-frequency contact ultrasonic debridement (LFCUD) on the bacterial load in hard-to-heal wounds in adults, compared with ultrasonic debridement alone. Secondary outcomes included wound healing, quality of life (QoL) and pain scores. METHOD: In this single-blinded, randomised, controlled trial participants were randomised to two groups. All participants received LFCUD weekly for six weeks, plus six weeks of weekly follow-up. The intervention group received an additional 15-minute topical application of PHMB post-LFCUD, at each dressing change and in a sustained dressing product. The control group received non-antimicrobial products and the wounds were cleansed with clean water or saline. Wound swabs were taken from all wounds for microbiological analysis at weeks 1, 3, 6 and 12. RESULTS: A total of 50 participants took part. The intervention group (n=25) had a lower bacterial load at week 12 compared with the control group (n=25) (p<0.001). There was no difference in complete wound healing between the groups (p=0.47) or wound-related QoL (p=0.15). However, more wounds deteriorated in the control group (44%) compared with the intervention group (8%, p=0.01). A higher proportion of wounds reduced in size in the intervention group (61% versus 12%, p=0.019). Pain was lower in the intervention group at week six, compared with controls (p=0.04). CONCLUSION: LFCUD without the addition of an antimicrobial agent such as PHMB, cannot be recommended. Further research requires longer follow-up time and would benefit from being powered sufficiently to test the effects of multiple covariates.

The Diagnosis and Management of Cardiometabolic Risk and Cardiometabolic Syndrome after Spinal Cord Injury.

Individuals with spinal cord injuries (SCI) commonly present with component risk factors for cardiometabolic risk and combined risk factors for cardiometabolic syndrome (CMS). These primary risk factors include obesity, dyslipidemia, dysglycemia/insulin resistance, and hypertension. Commonly referred to as "silent killers", cardiometabolic risk and CMS increase the threat of cardiovascular disease, a leading cause of death after SCI. This narrative review will examine current data and the etiopathogenesis of cardiometabolic risk, CMS, and cardiovascular disease associated with SCI, focusing on pivotal research on cardiometabolic sequelae from the last five years. The review will also provide current diagnosis and surveillance criteria for cardiometabolic disorders after SCI, a novel obesity classification system based on percent total body fat, and lifestyle management strategies to improve cardiometabolic health.

Characterization of an experimental model to determine streptococcal M protein-induced autoimmune cardiac and neurobehavioral abnormalities.

Group A streptococcal (GAS) infection is associated with a spectrum of autoimmune diseases including acute rheumatic fever/rheumatic heart disease (ARF/RHD) and neurobehavioral abnormalities. Antibodies against GAS M proteins cross-react with host tissue proteins in the heart and brain leading to the symptomatology observed in ARF/RHD. As throat carriage of Streptococcus dysgalactiae subspecies equisimilis (SDSE) has been reported to be relatively high in some ARF/RHD endemic regions compared with GAS, and both SDSE and GAS express coiled-coil surface protein called M protein, we hypothesized that streptococci other than GAS can also associated with ARF/RHD and neurobehavioral abnormalities. Neurobehavioral assessments and electrocardiography were performed on Lewis rats before and after exposure to recombinant GAS and SDSE M proteins. Histological assessments were performed to confirm inflammatory changes in cardiac and neuronal tissues. ELISA and Western blot analysis were performed to determine the cross-reactivity of antibodies with host connective, cardiac and neuronal tissue proteins. Lewis rats injected with M proteins either from GAS or SDSE developed significant cardiac functional and neurobehavioral abnormalities in comparison to control rats injected with phosphate-buffered saline. Antibodies against GAS and SDSE M proteins cross-reacted with cardiac, connective and neuronal proteins. Serum from rats injected with streptococcal antigens showed higher immunoglobulin G binding to the striatum and cortex of the brain. Cardiac and neurobehavioral abnormalities observed in our experimental model were comparable to the cardinal symptoms observed in patients with ARF/RHD. Here for the first time, we demonstrate in an experimental model that M proteins from different streptococcal species could initiate and drive the autoimmune-mediated cardiac tissue damage and neurobehavioral abnormalities.

Factors Affecting Dental Students' Comfort with Online Synchronous Learning.

Background: The COVID-19 pandemic caused many universities to expand their use of videoconferencing technology to continue academic coursework. This study examines dental students' experience, comfort levels, and preferences with videoconferencing. Methods: Of 100 s-year US dental students enrolled in a local anesthesia course, 54 completed a survey following an online synchronous lecture given in August 2020. Survey questions asked about prior experience with videoconferencing, comfort levels with online and traditional classes, and reasons for not turning on their video (showing their face). Results: Overall, 48.2% had little or no experience with videoconferencing prior to March 2020. Students were more comfortable with in-classroom parameters (listening, asking questions, answering questions, and interacting in small groups (breakouts)) than with online synchronous learning, although differences were not significant (p's > 0.10). Regression analyses showed there were significant positive associations between videoconferencing experience and comfort with both answering questions and interacting in breakouts (B = 0.55, p = 0.04 and B = 0.54, p = 0.03, respectively). Students reported being more comfortable during in-classroom breakouts than in breakouts using videoconferencing (p = 0.003). Main reasons for students not turning on their cameras were that they did not want to dress up (48.1%), other students were not using their video features (46.3%), and they felt they did not look good (35.5%). Conclusions: Dental students were somewhat more comfortable with traditional in-person vs. online classroom parameters. Prior experience with videoconferencing was associated with increased comfort with synchronous learning, suggesting that after the pandemic, it may be beneficial to structure dental school curricula as a hybrid learning experience with both in-person and online synchronous courses.

Energy expenditure and nutrient intake after spinal cord injury: a comprehensive review and practical recommendations.

Many persons with spinal cord injury (SCI) have one or more preventable chronic diseases related to excessive energetic intake and poor eating patterns. Appropriate nutrient consumption relative to need becomes a concern despite authoritative dietary recommendations from around the world. These recommendations were developed for the non-disabled population and do not account for the injury-induced changes in body composition, hypometabolic rate, hormonal dysregulation and nutrition status after SCI. Because evidence-based dietary reference intake values for SCI do not exist, ensuring appropriate consumption of macronutrient and micronutrients for their energy requirements becomes a challenge. In this compressive review, we briefly evaluate aspects of energy balance and appetite control relative to SCI. We report on the evidence regarding energy expenditure, nutrient intake and their relationship after SCI. We compare these data with several established nutritional guidelines from American Heart Association, Australian Dietary Guidelines, Dietary Guidelines for Americans, Institute of Medicine Dietary Reference Intake, Public Health England Government Dietary Recommendations, WHO Healthy Diet and the Paralyzed Veterans of America (PVA) Clinical Practice Guidelines. We also provide practical assessment and nutritional recommendations to facilitate a healthy dietary pattern after SCI. Because of a lack of strong SCI research, there are currently limited dietary recommendations outside of the PVA guidelines that capture the unique nutrient needs after SCI. Future multicentre clinical trials are needed to develop comprehensive, evidence-based dietary reference values specific for persons with SCI across the care continuum that rely on accurate, individual assessment of energy need.

Similar fat and carbohydrate oxidation in response to arm cycling exercise in persons with spinal cord injury versus able-bodied.

CONTEXT: Persons with spinal cord injury (SCI) present with low fat oxidation that is associated with poor cardiometabolic health. This study compared changes in fat and carbohydrate (CHO) oxidation during moderate intensity continuous exercise in persons with SCI and able-bodied adults (AB). DESIGN: Repeated measures, within-subjects study. SETTING: University laboratory in San Diego, CA. PARTICIPANTS: Nine men and women with SCI (age and time since injury = 32 ± 11 yr and 7 ± 6 yr) and 10 AB adults (age = 25 ± 8 yr). INTERVENTIONS: To assess peak oxygen uptake (VO2peak) and peak power output (PPO), participants performed progressive arm ergometry to volitional exhaustion. Subsequently, they completed 25 min of continuous exercise at 45%PPO. OUTCOME MEASURES: Respiratory exchange ratio (RER), fat and CHO oxidation, and blood lactate concentration (BLa) were assessed. RESULTS: Data showed a similar RER (P = 0.98) during exercise in SCI (0.97 ± 0.04) versus AB (0.97 ± 0.03) reflecting high CHO use and no differences in BLa (3.5 ± 1.1 and 3.0 ± 0.9 vs. mM, P = 0.56) or fat and CHO oxidation between groups (P > 0.05). However, participants with SCI exercised at a higher relative intensity (P < 0.01, 84 ± 7 vs. 75 ± 7%HRpeak) versus AB. CONCLUSION: Data confirm high reliance on CHO during arm ergometry in persons with SCI. To better compare substrate utilization to AB adults, we recommend that exercise be prescribed according to peak heart rate due to differences in cardiorespiratory fitness between groups.

Evaluation of three rapid low-resource molecular tests for Nipah virus.

Accurate and timely diagnosis of Nipah virus (NiV) requires rapid, inexpensive, and robust diagnostic tests to control spread of disease. Current state of the art technologies are slow and require laboratory infrastructure that may not be available in all endemic settings. Here we report the development and comparison of three rapid NiV molecular diagnostic tests based on reverse transcription recombinase-based isothermal amplification coupled with lateral flow detection. These tests include a simple and fast one-step sample processing step that inactivates the BSL-4 pathogen, enabling safe testing without the need for multi-step RNA purification. The rapid NiV tests targeted the Nucleocapsid protein (N) gene with analytical sensitivity down to 1,000 copies/µL for synthetic NiV RNA and did not cross-react with RNA of other flaviviruses or Chikungunya virus, which can clinically present with similar febrile symptoms. Two tests detected 50,000-100,000 TCID50/mL (100-200 RNA copies/reaction) of the two distinct strains of NiV, Bangladesh (NiVB) and Malaysia (NiVM), and took 30 min from sample to result, suggesting these tests are well suited for rapid diagnosis under resource-limited conditions due to rapidity, simplicity, and low equipment requirements. These Nipah tests represent a first step toward development of near-patient NiV diagnostics that are appropriately sensitive for first-line screening, sufficiently robust for a range of peripheral settings, with potential to be safely performed outside of biohazard containment facilities.

Cardiovascular autonomic nervous system function and hip fracture risk: the Cardiovascular Health Study.

Among 1299 older adults with 24-h Holter monitoring data at baseline, followed for approximately 15 years, 190 incident hip fractures occurred. Increased heart rate variability was independently associated with reduced risk of hip fracture among female participants. PURPOSE: Autonomic nervous system function modulates bone remodeling in rodent osteoporosis models. We tested whether cardiovascular autonomic function is associated with hip fracture risk in humans. METHODS: Participants were 1299 subjects from the Cardiovascular Health Study (mean age 72.8 years). Eight heart rate variability (HRV) measures (time and frequency domains, detrended fluctuation analysis variables, and heart rate turbulence) were derived from 24-h Holter monitor scans in sinus rhythm. Median follow-up for incident hip fracture was 14.7 years [IQR 9.1, 20.2]. Cox proportional hazards models were used to calculate hazard ratios (95% confidence intervals, CI). RESULTS: There were 144 hip fractures among 714 women (1.31 [1.06, 1.61] per 100-person years) and 46 among 585 men (0.62 [0.43, 0.90] per 100 person-years). From among HRV variables examined, a one standard deviation (SD) higher variation between normal heart beats over 24 h (the SD of NN intervals [SDNN]) was associated with a multivariable-adjusted lower hip fracture risk (HR [Formula: see text] 0.80; 95% CI 0.65-0.99; p = 0.04) in women. The adjusted association between very low frequency power, and hip fracture was borderline statistically significant in women (HR [Formula: see text] 0.82; 95% CI, 0.66-1.00; p = 0.06). When the 8 HRV variables were considered conjointly and adjusted for each other's association with hip fracture risk, a 1 SD higher SDNN value was significantly associated with reduced hip fracture risk in women (HR 0.74; 95% CI, 0.50-0.99; p = 0.05). No HRV variables were associated with hip fracture in men. CONCLUSIONS: In older women, increased heart rate variation is associated with hip fracture risk.