Lower limb control and mobility following exercise training

The objective of the present study was to evaluate the effects of 8-week balance or weight training on ankle joint stiffness and limb stability for older adults, furthermore, on outcomes of slips while walking. Eighteen older adults volunteered for the study and randomly were assigned to the three groups, such as, weight, balance, or control group. While walking on a walking track, three-dimensional posture data were sampled and ankle joint stiffness and limb stability were computed to evaluate the effects of training. 2 (pre and post) × 3 (weight, balance, and control) × 2 (dominant and non-dominant legs) mixed factor repeated ANOVA was performed. The results indicated that only balance training group showed an improvement in joint stiffness and both the training groups showed improvements in limb stability. Also, fall frequency results suggested that joint stiffness and limb stability had an effect on the likelihood of slip-induced falls. In conclusion, training can facilitate improvements in joint and limb control mechanism for older adults contributing to an improvement in the likelihood of slip-induced falls

The effects of 10% front load carriage on the likelihood of slips and falls

The objective of the present study was to evaluate if anterior load carriage would increase the likelihood of slips or falls while walking over a slippery floor surface. The study hypothesized that anterior load carriage may alter spatial-temporal characteristics, such as heel contact velocity, walking velocity (i.e., the whole body center-of-mass velocity), and step length, as well as friction demand characteristics at shoe-floor interface. Additionally, the study hypothesized that alterations in these gait parameters may influence slip initiation characteristics while ambulating over a slippery floor surface. Total of 10 subjects participated in the study: 5 younger (18-28 yr old) and 5 older adults (65 and older). A mixture was used to manipulate the coefficient of friction (COF) of the floor surface. All participants were unexpectedly introduced to a slippery surface while walking with and without a load. To evaluate slip severity, slip distance I and II were evaluated to assess whether a subject fell or not. Three-way repeated measure ANOVA (mix-factor design) was performed: Age factor: between-subject, Load and Floor factors: within-subject. Overall, older adults' heel contact velocity was slower while carrying a load. Additionally, all participants exhibited shorter SL while carrying a load. No significant friction demand characteristic differences were observed for all subjects while carrying a 10% front load. The results from the present study suggest that carrying 10% of the body weight in front should not intensify the slip propensity and severity although appears to influence spatial-temporal gait characteristics

Effects of Sound on Postural Stability during Quiet Standing

Loss of postural stability can increase the likelihood of slips and falls in workplaces. The present study intended to extend understanding of the effects of frequency and pressure level of sound on postural stability during standing. Eleven male subjects participated. Standing on a force platform, the subjects' center of pressures were measured under different combinations of pressure level and frequency of the sound. Variables such as the position variability of COP and the length of postural sway path in anterior-posterior (AP) and medio-lateral (ML) direction were evaluated. Subjective ratings of perceived disturbance at each experimental condition were also obtained using a 7-point rating scale. Results showed that the length of sway path and the position variability of COP increased as the frequency of sound increased in posterior-anterior axis. The effect of sound pressure level, however, was not significant on both the postural sway length and the position variability of COP. These results suggested substantial disturbance of standing balance system among subjects exposed to high frequency noise. The results implied that physical workers should be alerted that their abilities of postural balance could be degraded significantly as disturbance caused by a sound existed

Comparison of opioid prescribing by dentists in the United States and England

Importance: The United States consumes most of the opioids worldwide despite representing a small portion of the world\u27s population. Dentists are one of the most frequent US prescribers of opioids despite data suggesting that nonopioid analgesics are similarly effective for oral pain. While oral health and dentist use are generally similar between the United States and England, it is unclear how opioid prescribing by dentists varies between the 2 countries. Objective: To compare opioid prescribing by dentists in the United States and England. Design, Setting, and Participants: Cross-sectional study of prescriptions for opioids dispensed from outpatient pharmacies and health care settings between January 1 and December 31, 2016, by dentists in the United States and England. Data were analyzed from October 2018 to January 2019. Exposures: Opioids prescribed by dentists. Main Outcomes and Measures: Proportion and prescribing rates of opioid prescriptions. Results: In 2016, the proportion of prescriptions written by US dentists that were for opioids was 37 times greater than the proportion written by English dentists. In all, 22.3% of US dental prescriptions were opioids (11.4 million prescriptions) compared with 0.6% of English dental prescriptions (28 082 prescriptions) (difference, 21.7%; 95% CI, 13.8%-32.1%; P \u3c .001). Dentists in the United States also had a higher number of opioid prescriptions per 1000 population (35.4 per 1000 US population [95% CI, 25.2-48.7 per 1000 population] vs 0.5 per 1000 England population [95% CI, 0.03-3.7 per 1000 population]) and number of opioid prescriptions per dentist (58.2 prescriptions per dentist [95% CI, 44.9-75.0 prescriptions per dentist] vs 1.2 prescriptions per dentist [95% CI, 0.2-5.6 prescriptions per dentist]). While the codeine derivative dihydrocodeine was the sole opioid prescribed by English dentists, US dentists prescribed a range of opioids containing hydrocodone (62.3%), codeine (23.2%), oxycodone (9.1%), and tramadol (4.8%). Dentists in the United States also prescribed long-acting opioids (0.06% of opioids prescribed by US dentists [6425 prescriptions]). Long-acting opioids were not prescribed by English dentists. Conclusions and Relevance: This study found that in 2016, dentists in the United States prescribed opioids with significantly greater frequency than their English counterparts. Opioids with a high potential for abuse, such as oxycodone, were frequently prescribed by US dentists but not prescribed in England. These results illustrate how 1 source of opioids differs substantially in the United States vs England. To reduce dental opioid prescribing in the United States, dentists could adopt measures similar to those used in England, including national guidelines for treating dental pain that emphasize prescribing opioids conservatively

Mutations in TAC1B: a Novel Genetic Determinant of Clinical Fluconazole Resistance in Candida auris

Candida auris is an emerging multidrug-resistant pathogen of global concern, known to be responsible for outbreaks on six continents and to be commonly resistant to antifungals. While the vast majority of clinical C. auris isolates are highly resistant to fluconazole, an essential part of the available antifungal arsenal, very little is known about the mechanisms contributing to resistance. In this work, we show that mutations in the transcription factor TAC1B significantly contribute to clinical fluconazole resistance. These studies demonstrated that mutations in TAC1B can arise rapidly in vitro upon exposure to fluconazole and that a multitude of resistance-associated TAC1B mutations are present among the majority of fluconazole-resistant C. auris isolates from a global collection and appear specific to a subset of lineages or clades. Thus, identification of this novel genetic determinant of resistance significantly adds to the understanding of clinical antifungal resistance in C. auris.Candida auris has emerged as a multidrug-resistant pathogen of great clinical concern. Approximately 90% of clinical C. auris isolates are resistant to fluconazole, the most commonly prescribed antifungal agent, and yet it remains unknown what mechanisms underpin this fluconazole resistance. To identify novel mechanisms contributing to fluconazole resistance in C. auris, fluconazole-susceptible C. auris clinical isolate AR0387 was passaged in media supplemented with fluconazole to generate derivative strains which had acquired increased fluconazole resistance in vitro. Comparative analyses of comprehensive sterol profiles, [3H]fluconazole uptake, sequencing of C. auris genes homologous to genes known to contribute to fluconazole resistance in other species of Candida, and relative expression levels of C. aurisERG11, CDR1, and MDR1 were performed. All fluconazole-evolved derivative strains were found to have acquired mutations in the zinc-cluster transcription factor-encoding gene TAC1B and to show a corresponding increase in CDR1 expression relative to the parental clinical isolate, AR0387. Mutations in TAC1B were also identified in a set of 304 globally distributed C. auris clinical isolates representing each of the four major clades. Introduction of the most common mutation found among fluconazole-resistant clinical isolates of C. auris into fluconazole-susceptible isolate AR0387 was confirmed to increase fluconazole resistance by 8-fold, and the correction of the same mutation in a fluconazole-resistant isolate, AR0390, decreased fluconazole MIC by 16-fold. Taken together, these data demonstrate that C. auris can rapidly acquire resistance to fluconazole in vitro and that mutations in TAC1B significantly contribute to clinical fluconazole resistance

Phase II trial of levocetirizine with capecitabine and bevacizumab to overcome the resistance of antiangiogenic therapies in refractory metastatic colorectal cancer

Background: Despite the clinical success of vascular endothelial growth factor (VEGF) blockade in metastatic colorectal cancers (mCRC), resistance to anti-angiogenic drugs invariably develops. IL-8 and other cytokines have been implicated in development of resistance to anti-angiogenic therapy. Levocetirizine is a second generation H1 antihistamine with anti-inflammatory and IL-8 suppression properties. We conducted a phase II trial combining levocetirizine with capecitabine and bevacizumab to potentially overcome anti-angiogenic therapy resistance in patients with refractory mCRC. Methods: This was a single-center open-label prospective trial in refractory mCRC patients. Treatment consisted of oral capecitabine 850 mg/m Results: Forty-seven patients were enrolled in the trial to have 36 evaluable patients. Arm A enrolled 23 patients and Arm B enrolled 24 patients. Fifty percent of patients had progressive disease and 62% of patients had stable disease in each arm as best response. There was no demonstrable difference in PFS between the two arms (log-rank test P=0.83). Median time to progression was 3.4 months in Arm A and 3.5 months in Arm B. Conclusions: Median PFS in the trial was comparable to and appeared to be better than other regimens used in the refractory setting (e.g., median PFS of 1.9 months for regorafenib). Cytokine measurement with IL-8 levels did not show any correlation with progression free survival but patients with stable disease showed overall lower levels of IL-8 as compared to patients with progressive disease in the cytokine analysis

Monopoles over 4-manifolds containing long necks, I

We study moduli spaces of Seiberg-Witten monopoles over spin^c Riemannian 4-manifolds with long necks and/or tubular ends. This first part discusses compactness, exponential decay, and transversality. As applications we prove two vanishing theorems for Seiberg-Witten invariants.Comment: Published by Geometry and Topology at http://www.maths.warwick.ac.uk/gt/GTVol9/paper1.abs.htm

Sweetened Drink and Snacking Cues in Adolescents. A Study Using Ecological Momentary Assessment

The objective of this study was to identify physical, social, and intrapersonal cues that were associated with the consumption of sweetened beverages and sweet and salty snacks among adolescents from lower SES neighborhoods. Students were recruited from high schools with a minimum level of 25% free or reduced cost lunches. Using ecological momentary assessment, participants (N=158) were trained to answer brief questionnaires on handheld PDA devices: (a) each time they ate or drank, (b) when prompted randomly, and (c) once each evening. Data were collected over 7days for each participant. Participants reported their location (e.g., school grounds, home), mood, social environment, activities (e.g., watching TV, texting), cravings, food cues (e.g., saw a snack), and food choices. Results showed that having unhealthy snacks or sweet drinks among adolescents was associated with being at school, being with friends, feeling lonely or bored, craving a drink or snack, and being exposed to food cues. Surprisingly, sweet drink consumption was associated with exercising. Watching TV was associated with consuming sweet snacks but not with salty snacks or sweet drinks. These findings identify important environmental and intrapersonal cues to poor snacking choices that may be applied to interventions designed to disrupt these food-related, cue-behavior linked habits