Non-random genetic alterations in the cyanobacterium Nostoc sp. exposed to space conditions.

Understanding the impact of long-term exposure of microorganisms to space is critical in understanding how these exposures impact the evolution and adaptation of microbial life under space conditions. In this work we subjected Nostoc sp. CCCryo 231-06, a cyanobacterium capable of living under many different ecological conditions, and also surviving in extreme ones, to a 23-month stay at the International Space Station (the Biology and Mars Experiment, BIOMEX, on the EXPOSE-R2 platform) and returned it to Earth for single-cell genome analysis. We used microfluidic technology and single cell sequencing to identify the changes that occurred in the whole genome of single Nostoc cells. The variant profile showed that biofilm and photosystem associated loci were the most altered, with an increased variant rate of synonymous base pair substitutions. The cause(s) of these non-random alterations and their implications to the evolutionary potential of single bacterial cells under long-term cosmic exposure warrants further investigation.

Whole genome sequencing of cyanobacterium Nostoc sp. CCCryo 231-06 using microfluidic single cell technology.

The Nostoc sp. strain CCCryo 231-06 is a cyanobacterial strain capable of surviving under extreme conditions and thus is of great interest for the astrobiology community. The knowledge of its complete genome sequence would serve as a guide for further studies. However, a major concern has been placed on the effects of contamination on the quality of sequencing data without a reference genome. Here, we report the use of microfluidic technology combined with single cell sequencing and de novo assembly to minimize the contamination and recover the complete genome of the Nostoc strain CCCryo 231-06 with high quality. 100% of the whole genome was recovered with all contaminants removed and a strongly supported phylogenetic tree. The data reported can be useful for comparative genomics for phylogenetic and taxonomic studies. The method used in this work can be applied to studies that require high-quality assemblies of genomes of unknown microorganisms.

Porphyromonas somerae Invasion of Endometrial Cancer Cells.

Recent evidence suggests an association between endometrial cancer and the understudied bacterial species Porphyromonas somerae. This association was demonstrated in previous work that indicated a significantly enriched abundance of P. somerae in the uterine microbiome of endometrial cancer patients. Given the known associations of the Porphyromonas genus and oral cancer, we hypothesized that P. somerae may play a similar pathogenic role in endometrial cancer via intracellular activity. Before testing our hypothesis, we first characterized P. somerae biology, as current background data is limited. These novel characterizations include growth curves in liquid medium and susceptibility tests to antibiotics. We tested our hypothesis by examining growth changes in response to 17ß-estradiol, a known risk factor for endometrial cancer, followed by metabolomic profiling in the presence and absence of 17ß-estradiol. We found that P. somerae exhibits increased growth in the presence of 17ß-estradiol of various concentrations. However, we did not find significant changes in metabolite levels in response to 17ß-estradiol. To study direct host-microbe interactions, we used in vitro invasion assays under hypoxic conditions and found evidence for intracellular invasion of P. somerae in endometrial adenocarcinoma cells. We also examined these interactions in the presence of 17ß-estradiol but did not observe changes in invasion frequency. Invasion was shown using three lines of evidence including visualization via differential staining and brightfield microscopy, increased frequency of bacterial recovery after co-culturing, and in silico methods to detail relevant genomic and transcriptomic components. These results underscore potential intracellular phenotypes of P. somerae within the uterine microbiome. Furthermore, these results raise new questions pertaining to the role of P. somerae in the progression of endometrial cancer.

Gut and vaginal microbiomes on steroids: implications for women's health.

This review discusses the interactions of steroids with the gut and vaginal microbiomes within each life phase of adult women and the implications for women's health. Each phase of a woman's life is characterized by distinct hormonal states which drive overall physiology of both host and commensal microbes. These host-microbiome interactions underlie disease pathology in disorders that affect women across their lifetime, including bacterial vaginosis, gestational diabetes, polycystic ovary syndrome (PCOS), anxiety, depression, and obesity. Although many associations between host health and microbiome composition are well defined, the mechanistic role of the microbiome in women's health outcomes is largely unknown. This review addresses potential mechanisms by which the microbiota influences women's health and highlights gaps in current knowledge.

Efficient estimation of stereo thresholds: What slope should be assumed for the psychometric function?

Bayesian staircases are widely used in psychophysics to estimate detection thresholds. Simulations have revealed the importance of the parameters selected for the assumed subject's psychometric function in enabling thresholds to be estimated with small bias and high precision. One important parameter is the slope of the psychometric function, or equivalently its spread. This is often held fixed, rather than estimated for individual subjects, because much larger numbers of trials are required to estimate the spread as well as the threshold. However, if this fixed value is wrong, the threshold estimate can be biased. Here we determine the optimal slope to minimize bias and maximize precision when measuring stereoacuity with Bayesian staircases. We performed 2- and 4AFC disparity detection stereo experiments in order to measure the spread of the disparity psychometric function in human observers assuming a Logistic function. We found a wide range, between 0.03 and 3.5 log10 arcsec, with little change with age. We then ran simulations to examine the optimal spread using the empirical data. From our simulations and for three different experiments, we recommend selecting assumed spread values between the percentiles 60-80% of the population distribution of spreads (these percentiles can be extended to other type of thresholds). For stereo thresholds, we recommend a spread around the value σ = 1.7 log10 arcsec for 2AFC (slope ß = 4.3 /log10 arcsec), and around σ = 1.5 log10 arcsec for 4AFC (ß = 4.9 /log10 arcsec). Finally, we compared a Bayesian procedure (ZEST using the optimal σ) with five Bayesian procedures that are versions of ZEST-2D, Psi, and Psi-marginal. In general, for the conditions tested, ZEST optimal σ showed the lowest threshold bias and highest precision.

Complete Genome Sequences of Streptococcus sobrinus SL1 (ATCC 33478 = DSM 20742), NIDR 6715-7 (ATCC 27351), NIDR 6715-15 (ATCC 27352), and NCTC 10919 (ATCC 33402).

The bacterium Streptococcus sobrinus causes tooth decay in humans. We present complete circularized genome sequences for four strains of S. sobrinus, type strain SL1, strain NIDR 6715-7 and the related NIDR 6715-15, and strain NCTC 10919. The finished genomes will enable genomic comparisons between S. sobrinus and other cariogenic microbes.

Two choices good, four choices better: For measuring stereoacuity in children, a four-alternative forced-choice paradigm is more efficient than two.

PURPOSE: Measuring accurate thresholds in children can be challenging. A typical psychophysical experiment is usually too long to keep children engaged. However, a reduction in the number of trials decreases the precision of the threshold estimate. We evaluated the efficiency of forced-choice paradigms with 2 or 4 alternatives (2-AFC, 4-AFC) in a disparity detection experiment. 4-AFC paradigms are statistically more efficient, but also more cognitively demanding, which might offset their theoretical advantage in young children. METHODS: We ran simulations evaluating bias and precision of threshold estimates of 2-AFC and 4-AFC paradigms. In addition, we measured disparity thresholds in 43 children (aged 6 to 17 years) with a 4-AFC paradigm and in 49 children (aged 4 to 17 years) with a 2-AFC paradigm, both using an adaptive weighted one-up one-down staircase. RESULTS: Simulations indicated a similar bias and precision for a 2-AFC paradigm with double the number of trials as a 4-AFC paradigm. On average, estimated threshold of the simulated data was equal to the model threshold, indicating no bias. The precision was improved with an increasing number of trials. Likewise, our data showed a similar bias and precision for a 2-AFC paradigm with 60 trials as for a 4-AFC paradigm with 30 trials. Trials in the 4-AFC paradigm took slightly longer as participants scanned more alternatives. However, the 4-AFC task still ended up faster for a given precision. CONCLUSION: Bias and precision were similar in a 4-AFC task compared to a 2-AFC task with double the number of trials. However, a 4-AFC paradigm was more time efficient and is therefore recommended.

Contrast thresholds reveal different visual masking functions in humans and praying mantises.

Recently, we showed a novel property of the Hassenstein-Reichardt detector, namely that insect motion detection can be masked by 'undetectable' noise, i.e. visual noise presented at spatial frequencies at which coherently moving gratings do not elicit a response (Tarawneh et al., 2017). That study compared the responses of human and insect motion detectors using different ways of quantifying masking (contrast threshold in humans and masking tuning function in insects). In addition, some adjustments in experimental procedure, such as presenting the stimulus at a short viewing distance, were necessary to elicit a response in insects. These differences offer alternative explanations for the observed difference between human and insect responses to visual motion noise. Here, we report the results of new masking experiments in which we test whether differences in experimental paradigm and stimulus presentation between humans and insects can account for the undetectable noise effect reported earlier. We obtained contrast thresholds at two signal and two noise frequencies in both humans and praying mantises (Sphodromantis lineola), and compared contrast threshold differences when noise has the same versus different spatial frequency as the signal. Furthermore, we investigated whether differences in viewing geometry had any qualitative impact on the results. Consistent with our earlier finding, differences in contrast threshold show that visual noise masks much more effectively when presented at signal spatial frequency in humans (compared to a lower or higher spatial frequency), while in insects, noise is roughly equivalently effective when presented at either the signal spatial frequency or lower (compared to a higher spatial frequency). The characteristic difference between human and insect responses was unaffected by correcting for the stimulus distortion caused by short viewing distances in insects. These findings constitute stronger evidence that the undetectable noise effect reported earlier is a genuine difference between human and insect motion processing, and not an artefact caused by differences in experimental paradigms.

Invisible noise obscures visible signal in insect motion detection.

The motion energy model is the standard account of motion detection in animals from beetles to humans. Despite this common basis, we show here that a difference in the early stages of visual processing between mammals and insects leads this model to make radically different behavioural predictions. In insects, early filtering is spatially lowpass, which makes the surprising prediction that motion detection can be impaired by "invisible" noise, i.e. noise at a spatial frequency that elicits no response when presented on its own as a signal. We confirm this prediction using the optomotor response of praying mantis Sphodromantis lineola. This does not occur in mammals, where spatially bandpass early filtering means that linear systems techniques, such as deriving channel sensitivity from masking functions, remain approximately valid. Counter-intuitive effects such as masking by invisible noise may occur in neural circuits wherever a nonlinearity is followed by a difference operation.

Overestimation of stereo thresholds by the TNO stereotest is not due to global stereopsis.

PURPOSE: It has been repeatedly shown that the TNO stereotest overestimates stereo threshold compared to other clinical stereotests. In the current study, we test whether this overestimation can be attributed to a distinction between 'global' (or 'cyclopean') and 'local' (feature or contour-based) stereopsis. METHODS: We compared stereo thresholds of a global (TNO) and a local clinical stereotest (Randot Circles). In addition, a global and a local psychophysical stereotest were added to the design. One hundred and forty-nine children between 4 and 16 years old were included in the study. RESULTS: Stereo threshold estimates with TNO were a factor of two higher than with any of the other stereotests. No significant differences were found between the other tests. Bland-Altman analyses also indicated low agreement between TNO and the other stereotests, especially for higher stereo threshold estimates. Simulations indicated that the TNO test protocol and test disparities can account for part of this effect. DISCUSSION: The results indicate that the global - local distinction is an unlikely explanation for the overestimated thresholds of TNO. Test protocol and disparities are one contributing factor. Potential additional factors include the nature of the task (TNO requires depth discrimination rather than detection) and the use of anaglyph red/green 3D glasses rather than polarizing filters, which may reduce binocular fusion.

Health and economic benefits of physical activity for patients with spinal cord injury.

Spinal cord injury (SCI) is a traumatic, life-disrupting event with an annual incidence of 17,000 cases in the US. SCI is characterized by progressive physical deconditioning due to limited mobility and lack of modalities to allow safe physical activity that may partially offset these deleterious physical changes. Approximately, 50% of patients with SCI report no leisure-time physical activity and 15% report leisure-time physical activity below the threshold where meaningful health benefits could be realized. Collectively, about 363,000 patients with SCI, or 65% of the entire spinal cord injured population in the US, engages in insufficient physical activity and represents a target population that could derive considerable health benefits from even modest physical activity levels. Currently, the annual direct costs related to SCI exceed US$45 billion in the US. Rehabilitation protocols and technologies aimed to improve functional mobility have potential to significantly reduce the risk of medical complications and cost associated with SCI. Patients who commence routine physical activity in the first post-injury year and experience typical motor function improvements would realize US$290,000 to US$435,000 in lifetime cost savings, primarily due to fewer hospitalizations and less reliance on assistive care. New assistive technologies that allow patients with SCI to safely engage in routine physical activity are desperately needed.

Clinical effectiveness and safety of powered exoskeleton-assisted walking in patients with spinal cord injury: systematic review with meta-analysis.

BACKGROUND: Powered exoskeletons are designed to safely facilitate ambulation in patients with spinal cord injury (SCI). We conducted the first meta-analysis of the available published research on the clinical effectiveness and safety of powered exoskeletons in SCI patients. METHODS: MEDLINE and EMBASE databases were searched for studies of powered exoskeleton-assisted walking in patients with SCI. Main outcomes were analyzed using fixed and random effects meta-analysis models. RESULTS: A total of 14 studies (eight ReWalk™, three Ekso™, two Indego(®), and one unspecified exoskeleton) representing 111 patients were included in the analysis. Training programs were typically conducted three times per week, 60-120 minutes per session, for 1-24 weeks. Ten studies utilized flat indoor surfaces for training and four studies incorporated complex training, including walking outdoors, navigating obstacles, climbing and descending stairs, and performing activities of daily living. Following the exoskeleton training program, 76% of patients were able to ambulate with no physical assistance. The weighted mean distance for the 6-minute walk test was 98 m. The physiologic demand of powered exoskeleton-assisted walking was 3.3 metabolic equivalents and rating of perceived exertion was 10 on the Borg 6-20 scale, comparable to self-reported exertion of an able-bodied person walking at 3 miles per hour. Improvements in spasticity and bowel movement regularity were reported in 38% and 61% of patients, respectively. No serious adverse events occurred. The incidence of fall at any time during training was 4.4%, all occurring while tethered using a first-generation exoskeleton and none resulting in injury. The incidence of bone fracture during training was 3.4%. These risks have since been mitigated with newer generation exoskeletons and refinements to patient eligibility criteria. CONCLUSION: Powered exoskeletons allow patients with SCI to safely ambulate in real-world settings at a physical activity intensity conducive to prolonged use and known to yield health benefits.

The Stereoscopic Anisotropy Develops During Childhood.

PURPOSE: Human vision has a puzzling stereoscopic anisotropy: horizontal depth corrugations are easier to detect than vertical depth corrugations. To date, little is known about the function or the underlying mechanism responsible for this anisotropy. Here, we aim to find out whether this anisotropy is independent of age. To answer this, we compare detection thresholds for horizontal and vertical depth corrugations as a function of age. METHODS: The depth corrugations were defined solely by the horizontal disparity of random dot patterns. The disparities depicted a horizontal or vertical sinusoidal depth corrugation of spatial frequency 0.1 cyc/deg. Detection thresholds were obtained using Bayesian adaptive staircases from a total of 159 subjects aged from 3 to 73 years. For each participant we computed the anisotropy index, defined as the log10-ratio of the detection threshold for vertical corrugations divided by that for horizontal. RESULTS: Anisotropy index was highly variable between individuals but was positive in 87% of the participants. There was a significant correlation between anisotropy index and log-age (r = 0.21, P = 0.008) mainly driven by a significant difference between children and adults. In 67 children aged 3 to 13 years, the mean anisotropy index was 0.34 ± 0.38 (mean ± SD, meaning that vertical thresholds were on average 2.2 times the horizontal ones), compared with 0.59 ± 0.55 in 84 adults aged 18 to 73 years (vertical 3.9 times horizontal). This was mainly driven by a decline in the sensitivity to vertical corrugations. Children had poorer stereoacuity than adults, but had similar sensitivity to adults for horizontal corrugations and were actually more sensitive than adults to vertical corrugations. CONCLUSIONS: The fact that adults show stronger stereo anisotropy than children raises the possibility that visual experience plays a critical role in developing and strengthening the stereo anisotropy.

Clinical Perineal Streptococcal Infection in Children: Epidemiologic Features, Low Symptomatic Recurrence Rate after Treatment, and Risk Factors for Recurrence.

OBJECTIVES: To evaluate the epidemiology of perineal streptococcal infection and recurrence rates following amoxicillin treatment. STUDY DESIGN: We used laboratory logs in a single pediatric practice to identify patients 0-18 years of age with perineal cultures positive for group A Streptococcus (GAS) and reviewed their medical charts. We described epidemiologic features, determined recurrence rates following antibiotic treatment, and performed a case-control study to identify possible risk factors for recurrence in patients treated with amoxicillin. RESULTS: We found a perineal streptococcal infection rate of 4.6 per 10,000 patient encounters and a recurrence rate in 157 patients with perineal streptococcal infection of 12.4% after amoxicillin. In male patients, the predominant site of involvement was the perianal region (86%), and for female patients, the perivaginal area (62%). Nearly 80% of patients were 2-7 years of age (range 18 days-12.5 years). Perineal streptococcal infection and GAS pharyngitis followed a similar seasonal pattern of occurrence with 65% of perineal streptococcal infection occurring October through March. In patients with perineal streptococcal infection, 95% had a concomitant pharyngeal culture positive for GAS. Best predictive factors for recurrence after amoxicillin were longer duration of symptoms prior to diagnosis and having a sibling with perineal streptococcal infection at some time before or after the initial episode. CONCLUSIONS: Following treatment with amoxicillin, we found a low recurrence rate of 12.4%. Amoxicillin can be expected to be reliable first-line therapy for perineal streptococcal infection.

The contrast sensitivity function of the praying mantis Sphodromantis lineola.

The detection of visual motion and its direction is a fundamental task faced by several visual systems. The motion detection system of insects has been widely studied with the majority of studies focussing on flies and bees. Here we characterize the contrast sensitivity of motion detection in the praying mantis Sphodromantis lineola, an ambush predator that stays stationary for long periods of time while preying on fast-moving prey. In this, its visual behaviour differs from previously studied insects and we might therefore expect its motion detection system to differ from theirs. To investigate the sensitivity of the mantis we analyzed its optomotor response in response to drifting gratings with different contrasts and spatio-temporal frequencies. We find that the contrast sensitivity of the mantis depends on the spatial and temporal frequencies present in the stimulus and is separably tuned to spatial and temporal frequency rather than specifically to object velocity. Our results also suggest that mantises are sensitive to a broad range of velocities, in which they differ from bees and are more similar to hoverflies. We discuss our results in relation to the contrast sensitivities of other insects and the visual ecology of the mantis.

Relationship of obstructive sleep apnea and cardiometabolic risk factors in elderly patients with abdominal aortic aneurysm.

PURPOSE: This study seeks to determine the risks for obstructive sleep apnea (OSA) and cardiometabolic disease (CMR) in elderly patients with mild-moderate abdominal aortic aneurysms (AAA). METHODS: Three hundred two elderly patients with diagnosed small AAA disease were subjects. CMR was assessed by several biomarkers, with special focus on the Lipid Accumulation Product (LAP) and the Triglyceride-Glucose Index (TyG Index), two validated screening indicators of CMR related to central obesity and insulin resistance, respectively. Analysis of OSA risk was assessed with the Berlin Questionnaire. RESULTS: The patients (60.6 %) had increased risk of OSA; those at high risk also were at increased (p < 0.05) risk for CMR (15/25 biomarkers). CONCLUSIONS: As a group, elderly AAA patients are at risk for both OSA and cardiometabolic disease. Given that OSA and CMR may both amplify risk for AAA expansion, these patients should be screened for OSA, and when indicated, referred for definitive evaluation and treatment.

Comparison of patient attitudes and provider perceptions regarding medical student involvement in obstetric/gynecologic care.

BACKGROUND: Community physicians are becoming increasingly involved in clinical medical education. Some obstetrician/gynecologists have expressed reluctance to participate as clinical preceptors for medical students due to the sensitive nature of many of their patient encounters and concern for diminished patient satisfaction. PURPOSES: The purpose was to evaluate the willingness of community ob/gyn patients to participate in clinical medical education and to determine the accuracy of provider perceptions regarding this issue. METHODS: Surveys were distributed to women seeking ob/gyn care at 4 private practice sites in Tucson, Arizona. The surveys explored patient attitudes toward community physician involvement in clinical medical education as well as factors influencing personal willingness to include students as part of their healthcare team. Similar surveys were administered to the ob/gyn providers in those sites and evaluated their expectations of aggregate patient responses. RESULTS: Of 234 patient respondents, 87.6% believed that physicians have a responsibility to participate in medical education. Providers underestimated the number of patients for whom such participation would positively influence their personal provider choice (12.7% vs. 30.8%, p<.01) and overestimated negative (16.7% vs. 6.8%, p<.01) influence. Providers also underestimated acceptance rates of student pelvic examinations based on learner gender (13.8% vs. 24.3% male students, p=.01; 28.1% vs. 44.4% female students, p<.01). CONCLUSIONS: Patients in southern Arizona recognize and appreciate physicians' responsibility to educate future providers of women's healthcare. Providers may underestimate patient acceptance and value of students as part of their healthcare team. This bias may unnecessarily limit student exposure to clinical learning opportunities.

Association of Obstructive Sleep Apnea Severity with Exercise Capacity and Health-related Quality of Life.

BACKGROUND: Current research is inconclusive as to whether obstructive sleep apnea severity directly limits exercise capacity and lowers health-related quality of life (HRQoL). AIMS: The aim of this study was to evaluate the association of obstructive sleep apnea severity with determinants of exercise capacity and HRQoL. SUBJECTS AND METHODS: Subjects were evaluated by home somnography and classified as no obstructive sleep apnea (n = 43) or as having mild (n = 27), moderate or severe obstructive sleep apnea (n = 21). Exercise capacity was assessed by a ramping cycle ergometer test, and HRQoL was assessed with the SF-36 questionnaire. RESULTS: Greater obstructive sleep apnea severity was associated with older age, higher body weight, higher body mass index, lower peak aerobic capacity, a higher percentage of peak aerobic capacity at a submaximal exercise intensity of 55 watts, and lower physical component summary score from the SF-36. None of these variables were statistically different among obstructive sleep apnea severity groups after controlling for age and body weight. Obstructive sleep apnea severity was not associated with any cardiorespiratory fitness or HRQoL parameter. CONCLUSIONS: Obstructive sleep apnea severity has no independent association with exercise capacity or HRQoL.

Rationale, design and clinical performance of the mechanical response tissue analyser: a non-invasive technology for measurement of long bone bending stiffness.

Prediction of osteoporotic fractures is currently an imperfect science and new tools are desperately needed to identify at-risk patients at an earlier stage in the disease process. The mechanical response tissue analyser (MRTA) is a novel, non-invasive, radiation-free device that measures the bending stiffness of long bones in vivo, an indicator of a bone's ability to resist deformation under a given load and a strong predictor of long bone structural integrity and strength. Bone bending stiffness measured with the MRTA has been consistently shown to be a stronger predictor of post-mortem and ex vivo bone breaking strength compared to bone mineral measured with dual-energy X-ray absorptiometry. Bone bending stiffness measured with MRTA also decreases with advanced age and disease states and increases with chronic physical activity, independent of bone mineral changes. The MRTA measures different parameters than DXA (bone quality vs bone mineral content and density) and may be a more robust tool for identifying those at risk for fracture. Research initiatives focused on improving long-term repeatability and optimizing the signal-to-noise ratio of the measurement are currently underway to further advance the clinical usefulness of this technology.