Kaposi's Sarcoma Herpesvirus microRNAs Target Caspase 3 and Regulate Apoptosis

Kaposi's sarcoma herpesvirus (KSHV) encodes a cluster of twelve micro (mi)RNAs, which are abundantly expressed during both latent and lytic infection. Previous studies reported that KSHV is able to inhibit apoptosis during latent infection; we thus tested the involvement of viral miRNAs in this process. We found that both HEK293 epithelial cells and DG75 cells stably expressing KSHV miRNAs were protected from apoptosis. Potential cellular targets that were significantly down-regulated upon KSHV miRNAs expression were identified by microarray profiling. Among them, we validated by luciferase reporter assays, quantitative PCR and western blotting caspase 3 (Casp3), a critical factor for the control of apoptosis. Using site-directed mutagenesis, we found that three KSHV miRNAs, miR-K12-1, 3 and 4-3p, were responsible for the targeting of Casp3. Specific inhibition of these miRNAs in KSHV-infected cells resulted in increased expression levels of endogenous Casp3 and enhanced apoptosis. Altogether, our results suggest that KSHV miRNAs directly participate in the previously reported inhibition of apoptosis by the virus, and are thus likely to play a role in KSHV-induced oncogenesis

New Insight into the History of Domesticated Apple: Secondary Contribution of the European Wild Apple to the Genome of Cultivated Varieties

The apple is the most common and culturally important fruit crop of temperate areas. The elucidation of its origin and domestication history is therefore of great interest. The wild Central Asian species Malus sieversii has previously been identified as the main contributor to the genome of the cultivated apple (Malus domestica), on the basis of morphological, molecular, and historical evidence. The possible contribution of other wild species present along the Silk Route running from Asia to Western Europe remains a matter of debate, particularly with respect to the contribution of the European wild apple. We used microsatellite markers and an unprecedented large sampling of five Malus species throughout Eurasia (839 accessions from China to Spain) to show that multiple species have contributed to the genetic makeup of domesticated apples. The wild European crabapple M. sylvestris, in particular, was a major secondary contributor. Bidirectional gene flow between the domesticated apple and the European crabapple resulted in the current M. domestica being genetically more closely related to this species than to its Central Asian progenitor, M. sieversii. We found no evidence of a domestication bottleneck or clonal population structure in apples, despite the use of vegetative propagation by grafting. We show that the evolution of domesticated apples occurred over a long time period and involved more than one wild species. Our results support the view that self-incompatibility, a long lifespan, and cultural practices such as selection from open-pollinated seeds have facilitated introgression from wild relatives and the maintenance of genetic variation during domestication. This combination of processes may account for the diversification of several long-lived perennial crops, yielding domestication patterns different from those observed for annual species

Increased exercise tolerance using daytime mouthpiece ventilation for patients with diaphragm paralysis Case report

Mouthpiece ventilation can improve exercise tolerance in patients with unilateral or bilateral diaphragm paralysis http://ow.ly/X2Pd30dCT7n

A pilot study on the feasibility and effectiveness of treadmill-based perturbations for assessing and improving walking stability in chronic obstructive pulmonary disease

BACKGROUND: Falls risk is elevated in chronic obstructive pulmonary disease (COPD). However, there is a lack of evidence regarding the contributing factors. Here, we examined the feasibility of, and initial responses to, large walking perturbations in COPD, as well as the adaptation potential of people with COPD to repeated walking perturbations that might indicate potential for perturbation-based balance training in COPD. METHODS: 12 participants with COPD undergoing inpatient pulmonary rehabilitation and 12 age-gender-matched healthy control participants walked on an instrumented treadmill and experienced repeated treadmill-belt acceleration perturbations (leading to a forward balance loss). Three-dimensional motion capture was used to quantify the stability of participants body position during perturbed walking. Feasibility, stability following the initial perturbations and adaptation to repeated perturbations were assessed. FINDINGS: Using perturbations in this manner was feasible in this population (no harness assists and participants completed the minimum number of perturbations). No clear, specific deficit in reactive walking stability in COPD was found (no significant effects of participant group on stability or recovery step outcomes). There were mixed results for the adaptability outcomes which overall indicated some adaptability to repeated perturbations, but not to the same extent as the healthy control participants. INTERPRETATION: Treadmill-based perturbations during walking are feasible in COPD. COPD does not appear to result in significant deficits in stability following sudden perturbations and patients do demonstrate some adaptability to repeated perturbations. Perturbation-based balance training may be considered for fall prevention in research and practice in people with COPD

A pilot study on the feasibility and effectiveness of treadmill-based perturbations for assessing and improving walking stability in chronic obstructive pulmonary disease

BACKGROUND: Falls risk is elevated in chronic obstructive pulmonary disease (COPD). However, there is a lack of evidence regarding the contributing factors. Here, we examined the feasibility of, and initial responses to, large walking perturbations in COPD, as well as the adaptation potential of people with COPD to repeated walking perturbations that might indicate potential for perturbation-based balance training in COPD. METHODS: 12 participants with COPD undergoing inpatient pulmonary rehabilitation and 12 age-gender-matched healthy control participants walked on an instrumented treadmill and experienced repeated treadmill-belt acceleration perturbations (leading to a forward balance loss). Three-dimensional motion capture was used to quantify the stability of participants body position during perturbed walking. Feasibility, stability following the initial perturbations and adaptation to repeated perturbations were assessed. FINDINGS: Using perturbations in this manner was feasible in this population (no harness assists and participants completed the minimum number of perturbations). No clear, specific deficit in reactive walking stability in COPD was found (no significant effects of participant group on stability or recovery step outcomes). There were mixed results for the adaptability outcomes which overall indicated some adaptability to repeated perturbations, but not to the same extent as the healthy control participants. INTERPRETATION: Treadmill-based perturbations during walking are feasible in COPD. COPD does not appear to result in significant deficits in stability following sudden perturbations and patients do demonstrate some adaptability to repeated perturbations. Perturbation-based balance training may be considered for fall prevention in research and practice in people with COPD

Effects of Non-Invasive Ventilation Combined with Oxygen Supplementation on Exercise Performance in COPD Patients with Static Lung Hyperinflation and Exercise-Induced Oxygen Desaturation:A Single Blind, Randomized Cross-Over Trial

The effects of non-invasive ventilation (NIV) in addition to supplemental oxygen on exercise performance in patients with chronic obstructive pulmonary disease (COPD) with hyperinflation and exercise-induced desaturation (EID) remain unclear. We hypothesized that these patients would benefit from NIV and that this effect would be an add-on to oxygen therapy. Thirteen COPD patients with a residual volume >150% of predicted, normal resting arterial oxygen pressure (PaO2) and carbon-dioxide pressure (PaCO2) and EID during a six-minute walk test were included. Patients performed four constant work-rate treadmill tests, each consisting of two exercise bouts with a recovery period in between, wearing an oronasal mask connected to a ventilator and oxygen supply. The ventilator was set to the following settings in fixed order with clockwise rotation: Sham (continuous positive airway pressure (CPAP) 2 cm H2O, FiO2 21%), oxygen (CPAP 2 cm H2O, FiO2 35%), NIV and oxygen (inspiratory positive airway pressure (IPAP) 14 cm H2O/expiratory positive airway pressure (EPAP) 6 cm H2O, inspired oxygen fraction (FiO2) 35%), intermittent (walking: Sham setting, recovery: NIV and oxygen setting). During the first exercise, bout patients walked further with the oxygen setting compared to the sham setting (225 ± 107 vs 120 ± 50 meters, p < 0.05), but even further with the oxygen/NIV setting (283 ± 128 meters; p < 0.05). Recovery time between two exercise bouts was shortest with NIV and oxygen. COPD patients with severe static hyperinflation and EID benefit significantly from NIV in addition to oxygen during exercise and recovery

Wearable Finger Pulse Oximetry for Continuous Oxygen Saturation Measurements During Daily Home Routines of Patients With Chronic Obstructive Pulmonary Disease (COPD) Over One Week: Observational Study

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients can suffer from low blood oxygen concentrations. Peripheral blood oxygen saturation (SpO2), as assessed by pulse oximetry, is commonly measured during the day using a spot check, or continuously during one or two nights to estimate nocturnal desaturation. Sampling at this frequency may overlook natural fluctuations in SpO2. OBJECTIVE: This study used wearable finger pulse oximeters to continuously measure SpO2 during daily home routines of COPD patients and assess natural SpO2 fluctuations. METHODS: A total of 20 COPD patients wore a WristOx2 pulse oximeter for 1 week to collect continuous SpO2 measurements. A SenseWear Armband simultaneously collected actigraphy measurements to provide contextual information. SpO2 time series were preprocessed and data quality was assessed afterward. Mean SpO2, SpO2 SD, and cumulative time spent with SpO2 below 90% (CT90) were calculated for every (1) day, (2) day in rest, and (3) night to assess SpO2 fluctuations. RESULTS: A high percentage of valid SpO2 data (daytime: 93.27%; nocturnal: 99.31%) could be obtained during a 7-day monitoring period, except during moderate-to-vigorous physical activity (MVPA) (67.86%). Mean nocturnal SpO2 (89.9%, SD 3.4) was lower than mean daytime SpO2 in rest (92.1%, SD 2.9; P<.001). On average, SpO2 in rest ranged over 10.8% (SD 4.4) within one day. Highly varying CT90 values between different nights led to 50% (10/20) of the included patients changing categories between desaturator and nondesaturator over the course of 1 week. CONCLUSIONS: Continuous SpO2 measurements with wearable finger pulse oximeters identified significant SpO2 fluctuations between and within multiple days and nights of patients with COPD. Continuous SpO2 measurements during daily home routines of patients with COPD generally had high amounts of valid data, except for motion artifacts during MVPA. The identified fluctuations can have implications for telemonitoring applications that are based on daily SpO2 spot checks. CT90 values can vary greatly from night to night in patients with a nocturnal mean SpO2 around 90%, indicating that these patients cannot be consistently categorized as desaturators or nondesaturators. We recommend using wearable sensors for continuous SpO2 measurements over longer time periods to determine the clinical relevance of the identified SpO2 fluctuations.status: publishe

Wearable Finger Pulse Oximetry for Continuous Oxygen Saturation Measurements During Daily Home Routines of Patients With Chronic Obstructive Pulmonary Disease (COPD) Over One Week:Observational Study

Background: Chronic obstructive pulmonary disease (COPD) patients can suffer from low blood oxygen concentrations. Peripheral blood oxygen saturation (SpO(2)), as assessed by pulse oximetry, is commonly measured during the day using a spot check, or continuously during one or two nights to estimate nocturnal desaturation. Sampling at this frequency may overlook natural fluctuations in SpO(2). Objective: This study used wearable finger pulse oximeters to continuously measure SpO(2) during daily home routines of COPD patients and assess natural SpO(2) fluctuations. Methods: A total of 20 COPD patients wore a WristOx(2) pulse oximeter for 1 week to collect continuous SpO(2) measurements. A SenseWear Armband simultaneously collected actigraphy measurements to provide contextual information. SpO(2) time series were preprocessed and data quality was assessed afterward. Mean SpO(2) , SpO(2) SD, and cumulative time spent with SpO(2) below 90% (CT90) were calculated for every (1) day, (2) day in rest, and (3) night to assess SpO(2) fluctuations. Results: A high percentage of valid SpO(2) data (daytime: 93.27%; nocturnal: 99.31%) could be obtained during a 7-day monitoring period, except during moderate-to-vigorous physical activity (MVPA) (67.86%). Mean nocturnal SpO(2) (89.9%, SD 3.4) was lower than mean daytime SpO(2 )in rest (92.1%, SD 2.9; P Conclusions: Continuous SpO(2) measurements with wearable finger pulse oximeters identified significant SpO(2 )fluctuations between and within multiple days and nights of patients with COPD. Continuous SpO(2 ) measurements during daily home routines of patients with COPD generally had high amounts of valid data, except for motion artifacts during MVPA. The identified fluctuations can have implications for telemonitoring applications that are based on daily SpO(2) spot checks. CT90 values can vary greatly from night to night in patients with a nocturnal mean SpO(2) around 90%, indicating that these patients cannot be consistently categorized as desaturators or nondesaturators. We recommend using wearable sensors for continuous SpO(2 )measurements over longer time periods to determine the clinical relevance of the identified SpO(2 )fluctuations