Deep sequencing of 10,000 human genomes Telenti, Amalio; Pierce, Levi C. T.; Biggs, William H. ...
Proceedings of the National Academy of Sciences - PNAS,
10/2016, Letnik:
113, Številka:
42
Journal Article
Recenzirano
Odprti dostop
We report on the sequencing of 10,545 human genomes at 30×–40× coverage with an emphasis on quality metrics and novel variant and sequence discovery. We find that 84% of an individual human genome ...can be sequenced confidently. This high-confidence region includes 91.5% of exon sequence and 95.2% of known pathogenic variant positions. We present the distribution of over 150 million single-nucleotide variants in the coding and noncoding genome. Each newly sequenced genome contributes an average of 8,579 novel variants. In addition, each genome carries on average 0.7 Mb of sequence that is not found in the main build of the hg38 reference genome. The density of this catalog of variation allowed us to construct high-resolution profiles that define genomic sites that are highly intolerant of genetic variation. These results indicate that the data generated by deep genome sequencing is of the quality necessary for clinical use.
Advance care planning (ACP) is the process of ongoing communication among patients, family and health care professionals regarding what plans for future care are preferred in the event that patients ...become unable to make their own decisions. Clinicians play an important role in ACP as both initiators and decision coaches. However, lack of training for clinicians has frequently been reported as the reason for low involvement in ACP discussions - hence the present review evaluates the effectiveness of ACP training programs for healthcare professionals to guide the development of novel training programs for them in the future.
A literature search for intervention studies was conducted independently by two reviewers in July 2018. Participants included all healthcare professionals working with adult patients suffering from terminal illness. The primary outcomes were the professionals' knowledge of and attitudes towards ACP, and self-perceived competence in ACP conversations. The Effective Public Health Practice Project appraisal tool was used to examine the quality of the studies included.
A total of 4025 articles were identified, and ten eligible articles, covering 1081 participants, were included in the review. However, there is a lack of high quality randomized controlled trials of providing ACP training for nurses working in non-palliative care hospital settings. The overall quality of the intervention studies was moderate. All the studies included used instructional sessions in their interventions, while some contained group discussion, role-play and the use of advanced technology. The training programs increased the knowledge, attitudes towards shared decision-making, perceived communication skills, confidence, comfort and experiences concerned with discussing end-of-life (EOL) issues. Patient advocacy, job satisfaction and perceived level of adequate training for EOL care were improved. The use of 'decision aids' was rated as acceptable and clinically useful.
Training for healthcare professionals in ACP has positive effects on their knowledge, attitude and skills. The use of decision aids and advanced technology, instructional sessions with role play, training content focused on ACP communication skills and the needs and experience of patient in the ACP process, and a values-based ACP process are all those factors that made the ACP training programs effective.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains the leading cause of mortality from a single infectious agent. Each year around 9 million individuals newly develop active TB ...disease, and over 2 billion individuals are latently infected with M.tb worldwide, thus being at risk of developing TB reactivation disease later in life. The underlying mechanisms and pathways of protection against TB in humans, as well as the dynamics of the host response to M.tb infection, are incompletely understood. We carried out whole-genome expression profiling on a cohort of TB patients longitudinally sampled along 3 time-points: during active infection, during treatment, and after completion of curative treatment. We identified molecular signatures involving the upregulation of type-1 interferon (α/β) mediated signaling and chronic inflammation during active TB disease in an Indonesian population, in line with results from two recent studies in ethnically and epidemiologically different populations in Europe and South Africa. Expression profiles were captured in neutrophil-depleted blood samples, indicating a major contribution of lymphocytes and myeloid cells. Expression of type-1 interferon (α/β) genes mediated was also upregulated in the lungs of M.tb infected mice and in infected human macrophages. In patients, the regulated gene expression-signature normalized during treatment, including the type-1 interferon mediated signaling and a concurrent opposite regulation of interferon-gamma. Further analysis revealed IL15RA, UBE2L6 and GBP4 as molecules involved in the type-I interferon response in all three experimental models. Our data is highly suggestive that the innate immune type-I interferon signaling cascade could be used as a quantitative tool for monitoring active TB disease, and provide evidence that components of the patient's blood gene expression signature bear similarities to the pulmonary and macrophage response to mycobacterial infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sarcopenia, defined as a progressive loss of muscle mass and reduced muscle strength and functional capacity, is common among older adults. This study aimed to assess the proportion of people at risk ...of sarcopenia and probable sarcopenia among Chinese community-dwelling older adults living alone and to identify the associated factors. A total of 390 older adults were included in this study. Sarcopenia and probable sarcopenia were defined according to the criteria of the Asian Working Group for Sarcopenia 2019. Data on socio-demographic characteristics, health status, health behaviours and lifestyle characteristics, nutritional status, physical activity level, and depressive symptoms were collected. The association between these characteristics and sarcopenia risk was analysed using a multivariate ordinal logistic regression. The proportion of subjects at risk of sarcopenia and probable sarcopenia was found to be 57.7% and 30%, respectively. Older age, being malnourished and being at risk of malnutrition were significantly associated with sarcopenia risk. Being educated to secondary level or above, being overweight or obese and higher physical activity level were associated with decreased sarcopenia risk. Our results showed that older adults living alone were at high risk of developing sarcopenia and probable sarcopenia. These results emphasise the urgent need to initiate aggressive screening and holistic lifestyle therapeutic intervention strategies for this high-risk population.
Despite high rates of exposure, only 5-10% of people infected with Mycobacterium tuberculosis will develop active tuberculosis (TB) disease, suggesting a significant role for genetic variation in the ...human immune response to this infection. Here, we studied TB association and expression of 18 genes involved in the Toll-like receptor (TLR) pathways. Initially, we genotyped 149 sequence polymorphisms in 375 pulmonary TB patients and 387 controls from Indonesia. We found that four polymorphisms in the TLR8 gene on chromosome X showed evidence of association with TB susceptibility in males, including a non-synonymous polymorphism rs3764880 (Met1Val; P = 0.007, odds ratio (OR) = 1.8, 95% c.i. = 1.2-2.7). We genotyped these four TLR8 polymorphisms in an independent collection of 1,837 pulmonary TB patients and 1,779 controls from Russia and again found evidence of association in males (for rs3764880 P = 0.03, OR = 1.2, 95% c.i. = 1.02-1.48). Combined evidence for association is P = 1.2x10(-3)-6x10(-4). In addition, a quantitative PCR analysis indicated that TLR8 transcript levels are significantly up-regulated in patients during the acute phase of disease (P = 9.36x10(-5)), relative to baseline levels following successful chemotherapy. A marked increase in TLR8 protein expression was also observed directly in differentiated macrophages upon infection with M. bovis bacille Calmette-Guérin (BCG). Taken together, our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB across different populations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although China is undergoing rapid economic development, it is facing an ageing population. No data exists on malnutrition risks of older adults in an affluent Chinese society. The aim of this study ...is to examine these risks and identify their associated factors among home-living older Chinese adults in Hong Kong.
This is a cross-sectional study, to which home-living subjects aged 60 or above were recruited, between May and September 2017, from a non-governmental community organisation located in three different districts of Hong Kong. Nutritional status was assessed by the Mini Nutritional Assessment (MNA), and its associated factors examined included socio-demographic characteristics, lifestyle, health status and diet. Multivariable logistic regression analysis was performed to identify factors associated with malnutrition risks (MNA < 24).
Six hundred thirteen subjects (mean age: 78.5 ± 7.4; 54.0% females) completed the survey. Nearly 30% (n = 179) were at risk of malnutrition. By multivariable logistic regression, subjects (1) whose vision was only fair or unclear, (2) with poor usual appetite and (3) with main meal skipping behaviour had significantly higher malnutrition risk (all p < 0.05).
In this affluent Chinese society, the malnutrition risk in older adults is close to the global average, which is a matter for much concern. Interventions are therefore warranted that target vulnerable groups with poor vision, appetite, and meal skipping behaviour.
Not applicable.
Cardiovascular disease (CVD) is the leading cause of death worldwide. Studies using the a priori dietary pattern approach have been criticized for the heterogeneity of their scoring methods. This ...review aimed to evaluate the evidence on the association between a priori dietary patterns and CVD incidence in recent adult population-based studies. Similar to the conclusions of previous systematic reviews and meta-analyses, our review found that the majority of recent studies suggested that Mediterranean diet (6 out of 10 studies), Dietary Approaches to Stop Hypertension diet (4 out of 6 studies), Dietary Guidelines-based (11 out of 13 studies) patterns, and other emerging dietary patterns, including carbohydrate quality, Dietary Inflammatory Index, Plant-based Diet Index and Healthy Nordic Food Index, were cardioprotective in the general population; however, there was substantial heterogeneity among the studies, possibly due to differences in scoring methods and analytical approaches used and inclusion of different confounders, as well as other methodological drawbacks, such as low numbers of cases and short follow-up periods. Future studies should simultaneously examine and compare multiple a priori dietary patterns in a specific population using a uniform statistical approach. A consensus on the scoring methods for each a priori dietary pattern is also necessary.
To delineate the role of human papillomavirus (HPV) in laryngeal cancer in Southern Chinese, a retrospective cross‐sectional study was conducted in a major otorhinolaryngology referral center in Hong ...Kong. Eighty‐five Chinese patients with histology‐confirmed laryngeal squamous cell carcinoma (LSCC) diagnosed between 2005 and 2010 were examined for the status of HPV by PCR, and the expression of p16 and p53 by immunohistochemistry. The HPV, p16 and p53 findings were correlated with clinicopathological features, recurrence and 5‐year survival. HPV DNA was detected in one patient (1.2%, 95%CI: 0.2‐6.4%) who had glottic cancer and harbored HPV‐6. Overexpression of p16 and p53 were detected in 11 (12.9%) and 47 (55.3%) cases, respectively. Recurrence occurred in 22.4% of patients at a median of 13 months. The 5‐year overall survival and disease‐specific survival were 55.7% and 72.4%, respectively. Overexpression of p16 or p53 was not associated with clinicopathological features, recurrence or overall survival. HPV plays a limited role in laryngeal cancer in Hong Kong Southern Chinese. In contrast to oropharyngeal cancer, p16 cannot be used as a surrogate marker for oncogenic involvement of HPV and cannot predict survival in laryngeal cancer.
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