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Specific therapy involving non-small cell lung cancer.
o benefits of aging in place.The bacterial populations surviving in the presence of antibiotics contain cells that have gained genetic resistance, phenotypic resistance and tolerance to antibiotics. Isolation of live bacterial population, surviving against antibiotics, from the milieu of high proportions of dead/damaged cells will facilitate the study of the cellular/molecular processes used by them for survival. Here we present a Percoll gradient centrifugation based method for the isolation of enriched population of Mycobacterium smegmatis surviving in the presence of bactericidal concentrations of rifampicin and moxifloxacin. From the time of harvest, throughout the enrichment and isolation processes, and up to the lysis of the cells for total RNA preparation, we maintained the cells in the presence of the antibiotic to avoid changes in their metabolic status. The total RNA extracted from the enriched population of live antibiotic-surviving population showed structural integrity and purity. We analysed the transcriptome profile of the antibiotic-surviving population and compared it with the orthologue genes of Mycobacterium tuberculosis that conferred antibiotic tolerance on tubercle bacilli isolated from the tuberculosis patients under treatment with four antitubercular antibiotics. Statistically significant comparability between the gene expression profiles of the antibiotic tolerance associated genes of M. smegmatis and M. tuberculosis validated the reliability/utility of the method.
To assess the relation between social factors (socioeconomic status, household load and job strain) and chronic pain occurrence, and the role of gender in this relation.

We used data corresponding to 8 years of follow-up of the Stockholm Public Health Cohort Study (2006 to 2014) to compute Adjusted Incidence Rate Ratios (IRR) and additive interaction measures of chronic pain episodes, social factors, and sex in 16,687 subjects.

For men, increased rates were observed for skilled workers (IRR=1.27, 95% Confidence Interval (CI) 0.99, 1.61) and lower non-manual employees (IRR=1.37, 95%CI 1.05, 1.78), compared to unskilled workers; subjects with high household load (IRR=1.39; 95%CI 1.03, 1.88), compared to those with null score; and active jobs (IRR=1.27, 95%CI 1.06, 1.51), compared to low strain jobs. For women, we observed decreased rates for lower (IRR=0.82, 95%CI 0.68, 0.99), intermediate (IRR=0.74, 95%CI 0.63, 0.88) and higher non-manual employees (IRR=0.65, 95%CI 0.54, 0.79), compared to unskilled workers. Compared to subjects with a null score, women with low household load showed a lower rate (IRR=0.85; 95%CI 0.72, 1.00). Compared to low strain jobs, passive jobs (IRR=1.21; 95%CI 1.02, 1.44) and high strain jobs (IRR=1.46; 95%CI 1.02, 2.09) showed higher rates.

In general, our analysis yielded different results, if not opposite, when data were stratified by sex. Sex may then represent an effect modifier of the relation between social factors and chronic pain.

Low socioeconomic status and high job strain household load are related to chronic pain occurrence.Sex is an effect modifier of the relation between socioeconomic status and chronic pain; that is, this relation is different between men and women.
Low socioeconomic status and high job strain household load are related to chronic pain occurrence.Sex is an effect modifier of the relation between socioeconomic status and chronic pain; that is, this relation is different between men and women.Clinical studies have shown the efficacy of transcranial magnetic stimulation in treating movement disorders in patients with spinocerebellar ataxia (SCA). However, whether similar effects occur for their speech motor disorders remains largely unknown. The present event-related potential study investigated whether and how abnormalities in auditory-vocal integration associated with SCA can be modulated by neuronavigated continuous theta burst stimulation (c-TBS) over the right cerebellum. After receiving active or sham cerebellar c-TBS, 19 patients with SCA were instructed to produce sustained vowels while hearing their voice unexpectedly pitch-shifted by ±200 cents. Behaviorally, active cerebellar c-TBS led to smaller magnitudes of vocal compensations for pitch perturbations than sham stimulation. Parallel modulatory effects were also observed at the cortical level, as reflected by increased P1 and P2 responses but decreased N1 responses elicited by active cerebellar c-TBS. Moreover, smaller magnitudes of vocal compensations were predicted by larger amplitudes of cortical P1 and P2 responses. These findings provide the first neurobehavioral evidence that c-TBS over the right cerebellum produces modulatory effects on abnormal auditory-motor integration for vocal pitch regulation in patients with SCA, offering a starting point for the treatment of speech motor disorders associated with SCA with cerebellar c-TBS.Fundamental human feelings such as body ownership ("this" body is "my" body) and vicariousness (first-person-like experience of events occurring to others) are based on multisensory integration. Behavioral links between body ownership and vicariousness have been shown, but the neural underpinnings remain largely unexplored. To fill this gap, we investigated the neural effects of altered body ownership on vicarious somatosensation. While recording functional brain imaging data, first, we altered participants' body ownership by robotically delivering tactile stimulations ("tactile" stroking) in synchrony or not with videos of a virtual hand being brushed ("visual" stroking). Then, we manipulated vicarious somatosensation by showing videos of the virtual hand being touched by a syringe's plunger (touch) or needle (pain). Only after the alteration of body ownership (synchronous visuo-tactile stroking) and specifically during late epochs of vicarious somatosensation, vicarious pain was associated with lower activation in premotor and anterior cingulate cortices with respect to vicarious touch. At the methodological level, the present study highlights the importance of the neural response's temporal evolution. At the theoretical level, it shows that the higher-level (cognitive) impact of a lower-level (sensory) body-related processing (visuo-tactile) is not limited to body ownership but also extends to other psychological body-related domains, such as vicarious somatosensation.SWI/SNF chromatin remodeling complexes are key epigenetic regulators that are recurrently mutated in cancer. Most studies of these complexes are focused on their role in regulating protein-coding genes. However, here we show that SWI/SNF complexes control the expression of microRNAs. We used a SMARCA4-deficient model of lung adenocarcinoma (LUAD) to track changes in the miRNome upon SMARCA4 restoration. We found that SMARCA4-SWI/SNF complexes induced significant changes in the expression of cancer-related microRNAs. The most significantly dysregulated microRNA was miR-222, whose expression was promoted by SMARCA4-SWI/SNF complexes but not by SMARCA2-SWI/SNF complexes via their direct binding to a miR-222 enhancer region. Importantly, miR-222 expression decreased cell viability, phenocopying the tumor-suppressor role of SMARCA4-SWI/SNF complexes in LUAD. Finally, we showed that the miR-222 enhancer region resides in a topologically associated domain that does not contain any cancer-related protein-coding genes, suggesting that miR-222 may be involved in exerting the tumor suppressor role of SMARCA4. Overall, this study highlights the relevant role of the SWI/SNF complex in regulating the non-coding genome, opening new insights into the pathogenesis of LUAD.Inflammatory Bowel Diseases (IBD) such as Crohn's Disease (CD) and Ulcerative Colitis (UC) are complex conditions presenting with a wide range of phenotypes. Given major variation in disease severity and outcomes as well as response to existing therapies, a personalised treatment approach stands the chance of improving the overall disease outcome as well as minimising potentially harmful side effects. However, disease activity or distribution at the point of diagnosis are poor predictors of future disease outcome. Hence, the urgent need to develop biomarkers that could either predict the overall disease course (i.e. disease prognostic biomarkers) or the response to individual therapies (i.e. disease predictive biomarkers). Despite the widely accepted need for such biomarkers to improve the management of IBD patients, their development has proven to be challenging for a number of reasons. Based on our own experience in this field we perform a reality check on existing evidence, discuss main challenges and outline future perspectives.Chilling is a major stress to plants of subtropical and tropical origins including maize (Zea mays L.). To reveal molecular mechanisms underlying chilling tolerance and survival, we investigated transcriptomic responses to chilling stress in differentiated leaves and roots as well as in crowns with meristem activity in maize. Chilling stress on shoots and roots is found to each contributes to seedling lethality in maize. Comparison of maize lines with different chilling tolerance capacities reveals that chilling survival is highly associated with upregulation of abscisic acid biosynthesis and response as well as transcriptional regulators in leaves and crowns. It is also associated with the downregulation of translation in leaves and heat response in crowns. Chilling treatment on whole or part of the plants reveals that response to distal-chilling is very distinct from, and sometimes opposite to, response to local- or whole-plant chilling in both leaves and roots, suggesting a communication between shoots and roots in environmental response. This study thus provides transcriptomic responses in leaves, roots and crowns under differential chilling stresses in maize and reveals potential chilling tolerance and survival mechanisms which lays ground for improving chilling tolerance in crop plants.
Pulsed field ablation (PFA), a non-thermal ablative modality, may show different effects on the myocardial tissue compared to thermal ablation. Thus, this study aimed to compare the left atrial (LA) structural and mechanical characteristics after PFA vs. selleck inhibitor thermal ablation.

Cardiac magnetic resonance was performed pre-ablation, acutely (<3 h), and 3 months post-ablation in 41 patients with paroxysmal atrial fibrillation (AF) undergoing pulmonary vein (PV) isolation with PFA (n = 18) or thermal ablation (n = 23, 16 radiofrequency ablations, 7 cryoablations). Late gadolinium enhancement (LGE), T2-weighted, and cine images were analysed. In the acute stage, LGE volume was 60% larger after PFA vs. thermal ablation (P < 0.001), and oedema on T2 imaging was 20% smaller (P = 0.002). Tissue changes were more homogeneous after PFA than after thermal ablation, with no sign of microvascular damage or intramural haemorrhage. In the chronic stage, the majority of acute LGE had disappeared after PFA, whereas most LGE persisted after thermal ablation. The maximum strain on PV antra, the LA expansion index, and LA active emptying fraction declined acutely after both PFA and thermal ablation but recovered at the chronic stage only with PFA.

Pulsed field ablation induces large acute LGE without microvascular damage or intramural haemorrhage. Most LGE lesions disappear in the chronic stage, suggesting a specific reparative process involving less chronic fibrosis. This process may contribute to a preserved tissue compliance and LA reservoir and booster pump functions.
Pulsed field ablation induces large acute LGE without microvascular damage or intramural haemorrhage. Most LGE lesions disappear in the chronic stage, suggesting a specific reparative process involving less chronic fibrosis. This process may contribute to a preserved tissue compliance and LA reservoir and booster pump functions.
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