Background
Variations in healthcare provision around the world may impact how patients with functional gastrointestinal disorder (FGIDs) are investigated, diagnosed, and treated. However, these ...differences have not been reviewed.
Purposes
The Multinational Working Team of the Rome Foundation, established to make recommendations on the conduct of multinational, cross‐cultural research in FGIDs, identified seven key issues that are analyzed herein: (i) coverage afforded by different healthcare systems/providers; (ii) level of the healthcare system where patients with FGIDs are treated; (iii) extent/types of diagnostic procedures typically undertaken to diagnose FGIDs; (iv) physicians’ familiarity with and implementation of the Rome diagnostic criteria in clinical practice; (v) range of medications approved for FGIDs and approval process for new agents; (vi) costs involved in treating FGIDs; and (vii) prevalence and role of complementary/alternative medicine (CAM) for FGIDs. Because it was not feasible to survey all countries around the world, we compared a selected number of countries based on their geographical and ethno‐cultural diversity. Thus, we included Italy and South Korea as representative of nations with broad‐based coverage of healthcare in the population and India and Mexico as newly industrialized countries where there may be limited provision of healthcare for substantial segments of the population. In light of the paucity of formal publications on these issues, we included additional sources from the medical literature as well as perspectives provided by local experts and the media. Finally, we provide future directions on healthcare issues that should be taken into account and implemented when conducting cross‐cultural and multinational research in FGIDs.
This report identified seven key issues related to healthcare provision that may impact how patients with FGIDs are investigated, diagnosed, and managed. We compared four countries that are geographically and culturally diverse, and exhibit differences in the healthcare coverage provided to their population: Italy, South Korea, India, and Mexico. Future directions for conducting cross‐cultural and multinational research in FGIDs are provided.
Abstract Ventricular premature complexes (VPCs) during stress testing in the general population are commonly seen in clinical practice, but their prognostic value is not well understood. A ...comprehensive literature search of Medline, Embase, and the Cochrane Library between January 1970 and May 2015 was conducted. Observational cohort studies on general populations evaluating the association between exercise-induced VPCs and all-cause or cardiovascular mortality were included in the analysis. Nine studies comprising 62,488 participants comparing clinical outcomes of patients with and without exercise-induced VPCs were included. The overall combined relative risks for all-cause mortality and cardiovascular mortality in patients with exercise-induced VPCs were 1.41 (95% confidence interval CI: 1.23–1.61) and 1.86 (95% CI: 1.51–2.30), respectively. In subgroup analysis, both frequent VPCs (RR, 1.35; 95% CI, 1.14–1.60) and infrequent VPCs (RR, 1.57; 95% CI, 1.13–2.18) were associated with an adverse outcome. VPCs during recovery was associated with an increased risk of death (RR, 1.55; 95% CI, 1.22–1.96). VPCs during exercise did not achieve statistical significance (RR, 1.14; 95% CI, 0.96–1.34), but only a few studies were included in the analysis. In conclusion, our meta-analysis suggests that exercise-induced VPCs in the general population significantly increase the risk of total mortality and cardiovascular mortality. Our study calls for further studies to assess the prognostic significance of exercise-induced VPCs and the utility of efforts to reduce the VPC burden in order to improve the clinical outcome.
We have studied the role of core histone tails in the assembly of mitotic chromosomes using Xenopus egg extracts. Incubation of sperm nuclei in the extracts led to the formation of mitotic ...chromosomes, a process we found to be correlated with phosphorylation of the N‐terminal tail of histone H3 at Ser10. When the extracts were supplemented with H1‐depleted oligosomes, they were not able to assemble chromosomes. Selective elimination of oligosome histone tails by trypsin digestion resulted in a dramatic decrease in their ability to inhibit chromosome condensation. The chromosome assembly was also inhibited by each of the histone tails with differing efficiency. In addition, we found that nucleosomes were recruiting through the flexible histone tails some chromosome assembly factors, different from topoisomerase II and 13S condensin. These findings demonstrate that histone tails play an essential role in chromosome assembly. We also present evidence that the nucleosomes, through physical association, were able to deplete the extracts from the kinase phosphorylating histone H3 at Ser10, suggesting that this kinase could be important for chromosome condensation.
Cortical electrical stimulation (CES) has shown to be an effective therapeutic alternative for neuropathic pain refractory to pharmacological treatment. The primary motor cortex(M1) was the main ...cortical target used in the vast majority of both invasive and non-invasive studies. Despite positive results M1-based approaches still fail to relieve pain in a significant proportion of individuals. It has been advocated that the direct stimulation of cortical areas directly implicated in the central integration of pain could increase the efficacy of analgesic brain stimulation. Here, we evaluated the behavioral effects of electrical stimulation of the insular cortex (ESI) on pain sensitivity in an experimental rat model of peripheral neuropathy, and have described the pathways involved. Animals underwent chronic constriction of the sciatic nerve in the right hind limb and had concentric electrodes implanted in the posterior dysranular insular cortex. Mechanical nociception responses were evaluated before and at the end of a 15-min session of ESI (60Hz, 210μs, 1V). ESI reversed mechanical hypersensitivity in the paw contralateral to the brain hemisphere stimulated, without inducing motor impairment in the open-field test. Pharmacological blockade of μ-opioid (MOR) or type 1-cannabinoid receptors (CB1R) abolished ESI-induced antinociceptive effects. Evaluation of CB1R and MOR spatial expression demonstrated differential modulation of CB1R and MOR in the periaqueductal gray matter (PAG) of ESI-treated rats in sub-areas involved in pain processing/modulation. These results indicate that ESI induces antinociception by functionally modulating opioid and cannabinoid systems in the PAG pain circuitry in rats with experimentally induced neuropathic pain.
Summary
Background
Cross‐cultural, multinational research can advance the field of functional gastrointestinal disorders (FGIDs). Cross‐cultural comparative research can make a significant ...contribution in areas such as epidemiology, genetics, psychosocial modulators, symptom reporting and interpretation, extra‐intestinal co‐morbidity, diagnosis and treatment, determinants of disease severity, health care utilisation, and health‐related quality of life, all issues that can be affected by geographical region, culture, ethnicity and race.
Aims
To identify methodological challenges for cross‐cultural, multinational research, and suggest possible solutions.
Methods
This report, which summarises the full report of a working team established by the Rome Foundation that is available on the Internet, reflects an effort by an international committee of FGID clinicians and researchers. It is based on comprehensive literature reviews and expert opinion.
Results
Cross‐cultural, multinational research is important and feasible, but has barriers to successful implementation. This report contains recommendations for future research relating to study design, subject recruitment, availability of appropriate study instruments, translation and validation of study instruments, documenting confounders, statistical analyses and reporting of results.
Conclusions
Advances in study design and methodology, as well as cross‐cultural research competence, have not matched technological advancements. The development of multinational research networks and cross‐cultural research collaboration is still in its early stages. This report is intended to be aspirational rather than prescriptive, so we present recommendations, not guidelines. We aim to raise awareness of these issues and to pose higher standards, but not to discourage investigators from doing what is feasible in any particular setting.
Integration of high throughput DNA genotyping and RNA-sequencing data allows for the identification of genomic regions that control gene expression, known as expression quantitative trait loci ...(eQTL), on a whole genome scale. Intramuscular fat (IMF) content and carcass composition play important roles in metabolic and physiological processes in mammals because they influence insulin sensitivity and consequently prevalence of metabolic diseases such as obesity and type 2 diabetes. However, limited information is available on the genetic variants and mechanisms associated with IMF deposition in mammals. Thus, our hypothesis was that eQTL analyses could identify putative regulatory regions and transcription factors (TFs) associated with intramuscular fat (IMF) content traits.
We performed an integrative eQTL study in skeletal muscle to identify putative regulatory regions and factors associated with intramuscular fat content traits. Data obtained from skeletal muscle samples of 192 animals was used for association analysis between 461,466 SNPs and the transcription level of 11,808 genes. This yielded 1268 cis- and 10,334 trans-eQTLs, among which we identified nine hotspot regions that each affected the expression of > 119 genes. These putative regulatory regions overlapped with previously identified QTLs for IMF content. Three of the hotspots respectively harbored the transcription factors USF1, EGR4 and RUNX1T1, which are known to play important roles in lipid metabolism. From co-expression network analysis, we further identified modules significantly correlated with IMF content and associated with relevant processes such as fatty acid metabolism, carbohydrate metabolism and lipid metabolism.
This study provides novel insights into the link between genotype and IMF content as evident from the expression level. It thereby identifies genomic regions of particular importance and associated regulatory factors. These new findings provide new knowledge about the biological processes associated with genetic variants and mechanisms associated with IMF deposition in mammals.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Although symptoms of sleepiness and fatigue are common in adults with chronic kidney disease (CKD), little is known about the prevalence of these symptoms in children with CKD. Study ...Design Cross-sectional analysis within a cohort study. Setting & Participants We describe the frequency and severity of sleep problems and fatigue and assess the extent of their association with measured glomerular filtration rate (mGFR) and health-related quality of life (HRQOL) in 301 participants of the Chronic Kidney Disease in Children cohort. Outcomes & Measurements Sleep and fatigue-related items from the Pediatric Quality of Life Inventory 4.0 Generic Scales and the CKD-related Symptoms List were used. Results Median mGFR was 42.0 mL/min/1.73 m2 (25th-75th percentiles, 31.2-53.2), and median age was 13.9 years (25th-75th percentiles, 10.8-16.2). Children with mGFR of 40-<50, 30-<40, or <30 mL/min/1.73 m2 had 2.07 (95% CI, 1.05-4.09), 2.35 (95% CI, 1.17-4.72), and 2.59 (95% CI, 1.15-5.85) higher odds of having more severe parent reports of low energy than children with mGFR ≥ 50 mL/min/1.73 m2 . Compared with participants with mGFR ≥ 50 mL/min/1.73 m2 , those with mGFR < 30 mL/min/1.73 m2 had 3.92 (95% CI, 1.37-11.17) higher odds of reporting more severe weakness, and those with mGFR of 40-<50 mL/min/1.73 m2 had 2.95 (95% CI, 1.26-6.88) higher odds of falling asleep during the day. Low energy, trouble sleeping, and weakness were associated with lower HRQOL scores. Limitations Symptoms of sleep and fatigue represent the child's or parent's perception of symptom severity, whereas individual items can lead to imprecise measurements of sleep and fatigue. Conclusions Lower mGFR was associated with increased weakness, low energy, and daytime sleepiness. Furthermore, a strong association between trouble sleeping, low energy, and weakness with decreases in overall HRQOL was observed. Detection and treatment of poor sleep and fatigue may improve the development and HRQOL of children and adolescents with CKD.
Intramuscular fat (IMF) content is related to insulin resistance, which is an important prediction factor for disorders, such as cardiovascular disease, obesity and type 2 diabetes in human. At the ...same time, it is an economically important trait, which influences the sensorial and nutritional value of meat. The deposition of IMF is influenced by many factors such as sex, age, nutrition, and genetics. In this study Nellore steers (Bos taurus indicus subspecies) were used to better understand the molecular mechanisms involved in IMF content. This was accomplished by identifying differentially expressed genes (DEG), biological pathways and putative regulatory factors. Animals included in this study had extreme genomic estimated breeding value (GEBV) for IMF. RNA-seq analysis, gene set enrichment analysis (GSEA) and co-expression network methods, such as partial correlation coefficient with information theory (PCIT), regulatory impact factor (RIF) and phenotypic impact factor (PIF) were utilized to better understand intramuscular adipogenesis. A total of 16,101 genes were analyzed in both groups (high (H) and low (L) GEBV) and 77 DEG (FDR 10%) were identified between the two groups. Pathway Studio software identified 13 significantly over-represented pathways, functional classes and small molecule signaling pathways within the DEG list. PCIT analyses identified genes with a difference in the number of gene-gene correlations between H and L group and detected putative regulatory factors involved in IMF content. Candidate genes identified by PCIT include: ANKRD26, HOXC5 and PPAPDC2. RIF and PIF analyses identified several candidate genes: GLI2 and IGF2 (RIF1), MPC1 and UBL5 (RIF2) and a host of small RNAs, including miR-1281 (PIF). These findings contribute to a better understanding of the molecular mechanisms that underlie fat content and energy balance in muscle and provide important information for the production of healthier beef for human consumption.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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