Short-Course Therapy for Urinary Tract Infections in Children: The SCOUT Randomized Clinical Trial.

Importance: There is a paucity of pediatric-specific comparative data to guide duration of therapy recommendations in children with urinary tract infection (UTI). Objective: To compare the efficacy of standard-course and short-course therapy for children with UTI. Design, Setting, Participants: The Short Course Therapy for Urinary Tract Infections (SCOUT) randomized clinical noninferiority trial took place at outpatient clinics and emergency departments at 2 children's hospitals from May 2012, through, August 2019. Data were analyzed from January 2020, through, February 2023. Participants included children aged 2 months to 10 years with UTI exhibiting clinical improvement after 5 days of antimicrobials. Intervention: Another 5 days of antimicrobials (standard-course therapy) or 5 days of placebo (short-course therapy). Main Outcome Measures: The primary outcome, treatment failure, was defined as symptomatic UTI at or before the first follow-up visit (day 11 to 14). Secondary outcomes included UTI after the first follow-up visit, asymptomatic bacteriuria, positive urine culture, and gastrointestinal colonization with resistant organisms. Results: Analysis for the primary outcome included 664 randomized children (639 female [96%]; median age, 4 years). Among children evaluable for the primary outcome, 2 of 328 assigned to standard-course (0.6%) and 14 of 336 assigned to short-course (4.2%) had a treatment failure (absolute difference of 3.6% with upper bound 95% CI of 5.5.%). Children receiving short-course therapy were more likely to have asymptomatic bacteriuria or a positive urine culture at or by the first follow-up visit. There were no differences between groups in rates of UTI after the first follow-up visit, incidence of adverse events, or incidence of gastrointestinal colonization with resistant organisms. Conclusions and Relevance: In this randomized clinical trial, children assigned to standard-course therapy had lower rates of treatment failure than children assigned to short-course therapy. However, the low failure rate of short-course therapy suggests that it could be considered as a reasonable option for children exhibiting clinical improvement after 5 days of antimicrobial treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT01595529.

Elevated oxysterol and N-palmitoyl-O-phosphocholineserine levels in congenital disorders of glycosylation.

Congenital disorders of glycosylation (CDG) and Niemann-Pick type C (NPC) disease are inborn errors of metabolism that can both present with infantile-onset severe liver disease and other multisystemic manifestations. Plasma bile acid and N-palmitoyl-O-phosphocholineserine (PPCS) are screening biomarkers with proposed improved sensitivity and specificity for NPC. We report an infant with ATP6AP1-CDG who presented with cholestatic liver failure and elevated plasma oxysterols and bile acid, mimicking NPC clinically and biochemically. On further investigation, PPCS, but not the bile acid derivative N-(3ß,5α,6ß-trihydroxy-cholan-24-oyl) glycine (TCG), were elevated in plasma samples from individuals with ATP6AP1-, ALG1-, ALG8-, and PMM2-CDG. These findings highlight the importance of keeping CDG within the diagnostic differential when evaluating children with early onset severe liver disease and elevated bile acid or PPCS to prevent delayed diagnosis and treatment.

Making Choices-Newborn Male Circumcision.

Newborn male circumcision has potential benefits and advantages as well as disadvantages and risks. Families will at times have medical questions regarding newborn male circumcision that clinicians must be prepared to answer.

Predictors of perceived success in quitting smoking by vaping: A machine learning approach.

Prior research has suggested that a set of unique characteristics may be associated with adult cigarette smokers who are able to quit smoking using e-cigarettes (vaping). In this cross-sectional study, we aimed to identify and rank the importance of these characteristics using machine learning. During July and August 2019, an online survey was administered to a convenience sample of 889 adult smokers (age ≥ 20) in Ontario, Canada who tried vaping to quit smoking in the past 12 months. Fifty-one person-level characteristics, including a Vaping Experiences Score, were assessed in a gradient boosting machine model to classify the status of perceived success in vaping-assisted smoking cessation. This model was trained using cross-validation and tested using the receiver operating characteristic (ROC) curve. The top five most important predictors were identified using a score between 0% and 100% that represented the relative importance of each variable in model training. About 20% of participants (N = 174, 19.6%) reported success in vaping-assisted smoking cessation. The model achieved relatively high performance with an area under the ROC curve of 0.865 and classification accuracy of 0.831 (95% CI [confidence interval] 0.780 to 0.874). The top five most important predictors of perceived success in vaping-assisted smoking cessation were more positive experiences measured by the Vaping Experiences Score (100%), less previously failed quit attempts by vaping (39.0%), younger age (21.9%), having vaped 100 times (16.8%), and vaping shortly after waking up (15.8%). Our findings provide strong statistical evidence that shows better vaping experiences are associated with greater perceived success in smoking cessation by vaping. Furthermore, our study confirmed the strength of machine learning techniques in vaping-related outcomes research based on observational data.

Real-world vaping experiences and smoking cessation among cigarette smoking adults.

INTRODUCTION: E-cigarettes may have the potential to be an effective cessation aid for some cigarette smokers. However, the extent to which smokers' experiences using e-cigarettes (vaping) to quit smoking impact their cessation outcomes is unclear. In this cross-sectional survey study, we develop a multidimensional measure of vaping experiences in adults who quit smoking by vaping and test its association with perceived success in smoking cessation. METHODS: In 2019, recruitment invitations were emailed to adult past-year smokers who had accessed cessation services across Ontario, Canada. Respondents who tried vaping to quit smoking in the past year completed a detailed online survey. Factor analysis was performed on ratings of 45 vaping experiences items to identify dimensions of vaping experiences. Factor scores were entered into logistic regressions to test if vaping experiences dimensions had differential impact on perceived success in smoking cessation. RESULTS: Of the 889 participants, 56.0% were female, 81.1% were Caucasian, and the mean age was 37.7 ± 11.9 years. Twenty percent (19.6%) reported having successfully quit smoking by vaping in the past year. Among the six vaping experiences factors, better experiences in five factors-Relationships, Flexibility of Vaping, Side Effects, Vaping Devices, and Sensory Functions-were each independently and positively associated with improved odds of successful quitting. Notably, Relationships [OR = 2.01, 95% CI: 1.61-2.64] and Side Effects [OR = 1.95; 95% CI 1.54-2.29] were the strongest correlates of perceived success in smoking cessation. CONCLUSIONS: These findings indicate an opportunity to increase cessation rates by improving the experiences of smokers who vape to quit smoking.

Co-use and Mixing Tobacco With Cannabis Among Ontario Adults.

INTRODUCTION: The legalization of nonmedical cannabis in 2018 may have important implications for tobacco use in Canada. There is a risk of renormalizing tobacco use with co-use of tobacco and cannabis introducing nontobacco users to tobacco. Co-use is the use of both substances by the same individual at the same time or on different occasions, as well as mixed together. This study assessed the prevalence of co-use and mixing of tobacco and cannabis among Ontario adults and the characteristics of the users. AIMS AND METHODS: Data from the 1996 to 2017 cycles of the Centre for Addiction and Mental Health Monitor (n = 4481) were used to examine trends in prevalence and the proportion of Ontario adults co-using and mixing tobacco and cannabis. Logistic regression was used to study associations between user characteristics and co-use and mixing. RESULTS: Co-use of cigarettes and cannabis among cannabis users declined from 59.8% in 1996 to 41.7% in 2017. Past-year e-cigarette use was the only predictor of co-use. From 2015 to 2017, 31.1% (95% confidence interval 27.0, 35.9) of Ontario adults who used cannabis reported mixing it with tobacco in the past year. Being white, past-year e-cigarette use, having moderate or high nicotine dependence, and having moderate or high risk for cannabis problems were significant predictors of mixing among cannabis users. CONCLUSION: Given the well-established negative health effects associated with tobacco use, alongside a growing evidence base for negative health effects of cannabis smoking, co-use and mixing could pose a considerable public health concern in the context of legalization. IMPLICATIONS: Considerable effort has been expended to reduce tobacco smoking. However, current efforts to reduce tobacco smoking may be diminished since this study found the prevalence of mixing tobacco and cannabis among cannabis users in Ontario to be higher than expected. Mixing tobacco and cannabis may introduce nontobacco smokers to tobacco, exposing them to health risks associated with both cannabis and tobacco smoke. Therefore, there is a need to monitor changes in tobacco use and understanding implications for tobacco control and cessation programs within the changing environment of cannabis legalization in Canada and other jurisdictions.

Perceived addiction to vaping among youth and young adult regular vapers.

BACKGROUND: The prevalence of e-cigarette use among youth and young adults has increased markedly in recent years; however, little is known about young people's perceptions of e-cigarette addiction. This study examines factors associated with self-reported addiction to e-cigarette use among this population. METHODS: In 2018, 1048 Canadians aged 16-25 years were recruited through online social media platforms to complete a survey. Quota sampling was used to oversample regular e-cigarette users (vaping at least weekly); these 578 regular users were included in this analysis. Self-perceived addiction was assessed by asking participants if they felt they were 'very', 'somewhat' or 'not at all' addicted to e-cigarettes. A proportional odds model was employed to identify factors associated with the ordinal outcome. RESULTS: Almost half of regular users perceived themselves to be 'not at all addicted', 41% felt they were 'somewhat addicted' and 13% felt they were very addicted to e-cigarettes. Women, former cigarette smokers, daily vapers and those vaping for more than a year were more likely to report higher levels of perceived addiction. Similarly, high sensation-seeking youth, those reading blogs and websites about vaping, those frequently dripping and those using higher nicotine strengths had a greater likelihood of higher perceived addiction than their respective counterparts. CONCLUSION: More than half of youth and young adult regular e-cigarette users felt they had some level of addiction. The findings identify possible opportunities for targeted programming for education and treatment, as well as potential opportunities for policy change such as maximum allowable nicotine strengths.

Is vaping cessation like smoking cessation? A qualitative study exploring the responses of youth and young adults who vape e-cigarettes.

INTRODUCTION: Young people are now seeking help to quit vaping. However, little is known about vaping cessation. To bridge the gap between the current state of research and the urgent need for interventions, practitioners have drawn upon smoking cessation models under the assumption that vaping and smoking are fairly similar. In this study, we sought to understand the nature and extent to which vaping is similar to smoking in order to inform the development of vaping cessation interventions for young people. METHODS: Seven focus groups were conducted between November 2019 and February 2020 among youth (ages 16-18) and young adults (ages 19-29) living in the Greater Toronto Area who self-identified as e-cigarette vapers and expressed interest in vaping cessation (n = 41). Focus groups were audio recorded, transcribed verbatim, and analyzed using thematic analysis methods. RESULTS: Perceived similarities between vaping and smoking emerged from participant narratives: three themes relating to barriers to quitting (social benefits, stress reduction, sensory and behavioural gratification), and three relating to reasons for quitting (financial loss, industry influence, dependence). However, there were also perceived differences that emerged: three themes relating to barriers to quitting vaping (enjoyment of flavours, convenience and discreetness, lack of self-awareness of vaping behaviours), and two relating to reasons for quitting vaping (lack of trusted information, perceived social acceptability). CONCLUSIONS: Although there is significant overlap between vaping and smoking, understanding perceived differences in barriers to quitting and reasons for quitting is critical to advancing vaping cessation research and practice among young people.

Sensor Anchoring Improves the Correlation Between Intramuscular Pressure and Muscle Tension in a Rabbit Model.

Intramuscular pressure (IMP) shows promise for estimating individual muscle tension in vivo. However, previous pressure measurements show high variability during isometric contraction and poor correlation with tension during dynamic contraction. We hypothesized that enhanced sensor anchoring/orientation would improve tension estimation and thus developed a novel pressure sensor with a barbed housing. Sensors were inserted into the tibialis anterior (TA) of New Zealand White rabbits (N = 8) both parallel and perpendicular to the fiber orientation. We measured muscle stress and IMP during both isometric and dynamic contractions. Passive stress showed good agreement for both insertion directions across muscle lengths (ICC > 0.8). Active stress and IMP agreement were good (ICC = 0.87 ± 0.04) for perpendicular insertions but poor (ICC = 0.21 ± 0.22) for parallel insertions across both dynamic contractions and isometric contractions within the muscle's range of motion. These findings support use of IMP measurements to estimate muscle tension across a range of contraction conditions.

Non-linear Scaling of Passive Mechanical Properties in Fibers, Bundles, Fascicles and Whole Rabbit Muscles.

Defining variations in skeletal muscle passive mechanical properties at different size scales ranging from single muscle fibers to whole muscles is required in order to understand passive muscle function. It is also of interest from a muscle structural point-of-view to identify the source(s) of passive tension that function at each scale. Thus, we measured passive mechanical properties of single fibers, fiber bundles, fascicles, and whole muscles in three architecturally diverse muscles from New Zealand White rabbits (n = 6) subjected to linear deformation. Passive modulus was quantified at sarcomere lengths across the muscle's anatomical range. Titin molecular mass and collagen content were also quantified at each size scale, and whole muscle architectural properties were measured. Passive modulus increased non-linearly from fiber to whole muscle for all three muscles emphasizing extracellular sources of passive tension (p < 0.001), and was different among muscles (p < 0.001), with significant muscle by size-scale interaction, indicating quantitatively different scaling for each muscle (p < 0.001). These findings provide insight into the structural basis of passive tension and suggest that the extracellular matrix (ECM) is the dominant contributor to whole muscle and fascicle passive tension. They also demonstrate that caution should be used when inferring whole muscle properties from reduced muscle size preparations such as muscle biopsies.

Predictors of E-Cigarette Initiation: Findings From the Youth and Young Adult Panel Study.

OBJECTIVES: Although previous studies have identified reasons why youth try e-cigarettes, longitudinal research is needed to identify predictors of e-cigarette initiation. This study assesses predictors of e-cigarette initiation among youth and young adults in the 2018-2019 Youth and Young Adult Panel Study. METHODS: This study examined the proportion of Canadian participants aged 16 to 25 (n = 137) reporting never use of e-cigarettes at baseline in 2018. Individuals were categorized as not initiated and initiated at 12-month follow-up. We examined demographic characteristics, substance use, health status, social influences and perception by initiation category. Adjusted odds ratios (AORs) were calculated using logistic regression models and multivariable logistic regression model. RESULTS: Among the 137 never e-cigarette users at baseline, 59% remained never users while 41% initiated use of e-cigarettes during the 12-month follow-up. The results of multivariable logistic regression analysis showed that regularly seeing anyone use e-cigarettes (AOR: 4.11; 95% CI: 1.04, 16.31) and seeing anyone use e-cigarettes very often or always at baseline (AOR: 4.54; 95% CI: 1.21, 17.01) is associated with initiating e-cigarette use among youth and young adults. CONCLUSION: The results revealed social influences to be the most important predictors of initiation among youth and young adults. Interventions to prevent youth and young adults from initiating e-cigarette use should expand from only focusing on peer use to reducing use in public space such as parks and recreational facilities.

Redistribution of nerve strain enables end-to-end repair under tension without inhibiting nerve regeneration.

End-to-end repair under no or low tension leads to improved outcomes for transected nerves with short gaps, compared to repairs with a graft. However, grafts are typically used to enable a tension-free repair for moderate to large gaps, as excessive tension can cause repairs to fail and catastrophically impede recovery. In this study, we tested the hypothesis that unloading the repair interface by redistributing tension away from the site of repair is a safe and feasible strategy for end-to-end repair of larger nerve gaps. Further, we tested the hypothesis that such an approach does not adversely affect structural and functional regeneration. In this study, we used a rat sciatic nerve injury model to compare the integrity of repair and several regenerative outcomes following end-to-end repairs of nerve gaps of increasing size. In addition, we proposed the use of a novel implantable device to safely repair end-to-end repair of larger nerve gaps by redistributing tension away from the repair interface. Our data suggest that redistriubution of tension away from the site of repair enables safe end-to-end repair of larger gap sizes. In addition, structural and functional measures of regeneration were equal or enhanced in nerves repaired under tension - with or without a tension redistribution device - compared to tension-free repairs. Provided that repair integrity is maintained, end-to-end repairs under tension should be considered as a reasonable surgical strategy. All animal experiments were performed under the approval of the Institutional Animal Care and Use Committee of University of California, San Diego (Protocol S11274).

Marketing IQOS in a dark market.

INTRODUCTION: Phillip Morris International (PMI) is pushing hard to promote IQOS heat-not-burn cigarettes in Ontario, Canada. Canada regulates IQOS as a tobacco product so that the robust tobacco marketing ban creates challenges to its promotion. METHODS: We collected data on IQOS promotion in 49 retail outlets, and through interviews with clerks and observations outside an IQOS store. RESULTS: The dominant marketing channel is the visible availability of IQOS in a large number of tobacco retail outlets-1029 across Ontario. Several stores display the price of 'heated tobacco' on one of three price signs which are permitted despite Ontario's total display ban. IQOS boutique stores are the locus of aggressive promotion including exchanging a pack of cigarettes or lighter for an IQOS device, launch parties, 'meet and greet' lunches and after-hour events. Outside the store, promotion includes a prominent IQOS sign, a sandwich board sign reading 'Building a Smoke-Free Future' and sales representatives regularly smoking IQOS. Membership services: Upon acquiring an IQOS device one can register to access the IQOS website store5 and receive customer support services, a map of retail locations and a product catalogue. Members receive regular email invitations to complete surveys with opportunities to win prizes. CONCLUSIONS: These promotion activities have undoubtedly made substantial numbers of Ontarians aware of IQOS. Yet, the government has not provided guidance as to absolute and relative potential harms. Our observations of tactics to promote a new tobacco product in a dark market may inform government regulatory policy and non-governmental organisation efforts wherever heat-not-burn products are introduced.

Is blue the new green? Repackaging menthol cigarettes in response to a flavour ban in Ontario, Canada.

BACKGROUND: As of 1 January 2017, the Canadian province of Ontario banned the distribution and sale of menthol tobacco products. There is limited knowledge about how tobacco companies will adapt their packaging in response to a menthol ban. METHODS: We conducted a content analysis of preban traditional menthol (no capsule) and menthol capsule cigarette packs and their postban replacements. Preban and postban packs were matched using tobacco company descriptions of replacement brands in business-to-business marketing materials, advertising on cigarette pack cellophane and a tobacco company website. RESULTS: A total of 63 menthol (n=30) and 'non-menthol alternative' (n=33) cigarette packs were included in the analysis. Approximately half of the preban packs were menthol capsule cigarettes and half traditional menthol cigarettes. While some postban brands continued to convey menthol-like qualities via the colour and/or brand descriptor 'green', 'blue' was the most common colour and brand descriptor postban. Packs shifted from using 'menthol' and/or 'fresh' as taste descriptor preban to using 'smooth' postban; some postban packs had 'non-menthol alternative' or 'without menthol/capsules' written on their cellophane. The presence of innovative filter technologies continued in the postban samples. CONCLUSION: Results suggest that tobacco companies attempted to maintain menthol smokers in Ontario by aggressive preban promotion of menthol capsule cigarettes, continued promotion of innovative filter technologies and by directing smokers to non-menthol alternatives whose packaging both in text and in colour connoted menthol-like qualities (eg, green) and reduced harshness or harm (eg, blue, white, silver, smooth taste).

Pelvic muscles' mechanical response to strains in the absence and presence of pregnancy-induced adaptations in a rat model.

BACKGROUND: Maternal birth trauma to the pelvic floor muscles is thought to be consequent to mechanical demands placed on these muscles during fetal delivery that exceed muscle physiological limits. The above is consistent with studies of striated limb muscles that identify hyperelongation of sarcomeres, the functional muscle units, as the primary cause of mechanical muscle injury and resultant muscle dysfunction. However, pelvic floor muscles' mechanical response to strains have not been examined at a tissue level. Furthermore, we have previously demonstrated that during pregnancy, rat pelvic floor muscles acquire structural and functional adaptations in preparation for delivery, which likely protect against mechanical muscle injury by attenuating the strain effect. OBJECTIVE: We sought to determine the mechanical impact of parturition-related strains on pelvic floor muscles' microstructure, and test the hypothesis that pregnancy-induced adaptations modulate muscle response to strains associated with vaginal delivery. STUDY DESIGN: Three-month-old Sprague-Dawley late-pregnant (N = 20) and nonpregnant (N = 22) rats underwent vaginal distention, replicating fetal crowning, with variable distention volumes. Age-matched uninjured pregnant and nonpregnant rats served as respective controls. After sacrifice, pelvic floor muscles, which include coccygeus, iliocaudalis, and pubocaudalis, were fixed in situ and harvested for fiber and sarcomere length measurements. To ascertain the extent of physiological strains during spontaneous vaginal delivery, analogous measurements were obtained in intrapartum rats (N = 4) sacrificed during fetal delivery. Data were compared with repeated measures and 2-way analysis of variance, followed by pairwise comparisons, with significance set at P < .05. RESULTS: Gross anatomic changes were observed in the pelvic floor muscles following vaginal distention, particularly in the entheseal region of pubocaudalis, which appeared translucent. The above appearance resulted from dramatic stretch of the myofibers, as indicated by significantly longer fiber length compared to controls. Stretch ratios, calculated as fiber length after vaginal distention divided by baseline fiber length, increased gradually with increasing distention volume. Paralleling these macroscopic changes, vaginal distention resulted in acute and progressive increase in sarcomere length with rising distention volume. The magnitude of strain effect varied by muscle, with the greatest sarcomere elongation observed in coccygeus, followed by pubocaudalis, and a smaller increase in iliocaudalis, observed only at higher distention volumes. The average fetal rat volume approximated 3 mL. Pelvic floor muscle sarcomere lengths in pregnant animals undergoing vaginal distention with 3 mL were similar to intrapartum sarcomere lengths in all muscles (P > .4), supporting the validity of our experimental approach. Vaginal distention resulted in dramatically longer sarcomere lengths in nonpregnant compared to pregnant animals, especially in coccygeus and pubocaudalis (P < .0001), indicating significant attenuation of sarcomere elongation in the presence of pregnancy-induced adaptations in pelvic floor muscles. CONCLUSION: Delivery-related strains lead to acute sarcomere elongation, a well-established cause of mechanical injury in skeletal muscles. Sarcomere hyperelongation resultant from mechanical strains is attenuated by pregnancy-induced adaptations acquired by the pelvic floor muscles prior to parturition.

A point of application study to determine the accuracy, precision and reliability of a low-cost balance plate for center of pressure measurement.

Changes in postural sway measured via force plate center of pressure have been associated with many aspects of human motor ability. A previous study validated the accuracy and precision of a relatively new, low-cost and portable force plate called the Balance Tracking System (BTrackS). This work compared a laboratory-grade force plate versus BTrackS during human-like dynamic sway conditions generated by an inverted pendulum device. The present study sought to extend previous validation attempts for BTrackS using a more traditional point of application (POA) approach. Computer numerical control (CNC) guided application of ∼155 N of force was applied five times to each of 21 points on five different BTrackS Balance Plate (BBP) devices with a hex-nose plunger. Results showed excellent agreement (ICC > 0.999) between the POAs and measured COP by the BBP devices, as well as high accuracy (<1% average percent error) and precision (<0.1 cm average standard deviation of residuals). The ICC between BBP devices was exceptionally high (ICC > 0.999) providing evidence of almost perfect inter-device reliability. Taken together, these results provide an important, static corollary to the previously obtained dynamic COP results from inverted pendulum testing of the BBP.

Lack of change in glucose metabolism in eszopiclone-treated primary insomnia patients.

STUDY OBJECTIVES: Primary insomnia (PI) may increase diabetes risk. We tested the hypothesis that the effects of PI on glucose metabolism could be improved by 2 months of pharmacological treatment. METHODS: Adult men and women meeting clinical criteria for PI were studied (n=20, body mass index 25.1±2.7 kg/m2, age 39.7±7.9) in a randomized, double-blind, placebo-controlled clinical trial. The study consisted of two 1-day inpatient admissions to a General Clinical Research Center separated by 2 months of at-home treatment with 3 mg eszopiclone or placebo. During inpatient admissions, each subject underwent two intravenous glucose tolerance tests (IVGTTs) pre- and post-treatment. Diet was controlled for micro- and macro-nutrient content and calories on the day prior to pre- and post-treatment IVGTTs. Subjects were randomized following completion of the initial IVGTT to take either placebo or eszopiclone 30 min prior to bedtime at home for 2 months. RESULTS: Two-month eszopiclone treatment did not change insulin sensitivity, glucose tolerance, or any of the sleep measures significantly, compared with placebo. Changes in glycated hemoglobin (HbA1c, clinical measure of glycemic control) were correlated with changes in diary-reported total sleep time in the eszopiclone group (r=0.66, p=0.0360), and in the combined groups' data (r=0.55, p=0.0125). Changes in polysomnography-measured wake after sleep onset, a hallmark of PI, were positively related to changes in IVGTT-derived glucose effectiveness, or non-insulin-mediated glucose uptake. CONCLUSION: Treatment with 3 mg eszopiclone for 2 months, compared with placebo, did not significantly influence either sleep or measures of diabetes risk in this preliminary study.

Contribution of blood oxygen and carbon dioxide sensing to the energetic optimization of human walking.

People can adapt their gait to minimize energetic cost, indicating that walking's neural control has access to ongoing measurements of the body's energy use. In this study we tested the hypothesis that an important source of energetic cost measurements arises from blood gas receptors that are sensitive to O2 and CO2 concentrations. These receptors are known to play a role in regulating other physiological processes related to energy consumption, such as ventilation rate. Given the role of O2 and CO2 in oxidative metabolism, sensing their levels can provide an accurate estimate of the body's total energy use. To test our hypothesis, we simulated an added energetic cost for blood gas receptors that depended on a subject's step frequency and determined if subjects changed their behavior in response to this simulated cost. These energetic costs were simulated by controlling inspired gas concentrations to decrease the circulating levels of O2 and increase CO2 We found this blood gas control to be effective at shifting the step frequency that minimized the ventilation rate and perceived exertion away from the normally preferred frequency, indicating that these receptors provide the nervous system with strong physiological and psychological signals. However, rather than adapt their preferred step frequency toward these lower simulated costs, subjects persevered at their normally preferred frequency even after extensive experience with the new simulated costs. These results suggest that blood gas receptors play a negligible role in sensing energetic cost for the purpose of optimizing gait.NEW & NOTEWORTHY Human gait adaptation implies that the nervous system senses energetic cost, yet this signal is unknown. We tested the hypothesis that the blood gas receptors sense cost for gait optimization by controlling blood O2 and CO2 with step frequency as people walked. At the simulated energetic minimum, ventilation and perceived exertion were lowest, yet subjects preferred walking at their original frequency. This suggests that blood gas receptors are not critical for sensing cost during gait.

In Vivo Sarcomere Length Measurement in Whole Muscles during Passive Stretch and Twitch Contractions.

Muscle force is dictated by micrometer-scale contractile machines called sarcomeres. Whole-muscle force drops from peak force production to zero with just a few micrometers of sarcomere length change. No current technology is able to capture adequate dynamic sarcomere data in vivo, and thus we lack fundamental data needed to understand human movement and movement disorders. Methods such as diffraction, endoscopy, and optical coherence tomography have been applied to muscle but are prohibitively invasive, sensitive to motion artifact, and/or imprecise. Here, we report dynamic sarcomere length measurement in vivo using a combination of our recently validated resonant reflection spectroscopy method combined with optical frequency domain interferometry. Using a 250-µm-wide fiber optic probe, we captured nanometer sarcomere length changes from thousands of sarcomeres on the sub-millisecond timescale during whole-muscle stretch and twitch contraction. We believe that this demonstrates the first large-scale sensing of sarcomere dynamics in vivo, which is a necessary first step to understand movement disorders and to create patient-specific surgical interventions and rehabilitation.