The Epidemiological Importance of Subclinical Tuberculosis. A Critical Reappraisal.
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ABSTRACT:
SUBMITTER: Kendall EA
PROVIDER: S-EPMC7874405 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Among the methods developed to detect H. pylori infection, determining the gold standard remains debatable, especially for epidemiological studies. Due to the decreasing sensitivity of direct diagnostic tests (histopathology and/or immunohistochemistry [IHC], rapid urease test [RUT], and culture), several indirect tests, including antibody-based tests (serology and urine test), urea breath test (UBT), and stool antigen test (SAT) have been developed to diagnose H. pylori infection. Among the indirect tests, UBT and SAT became the best methods to determine active infection. While antibody-based tests, especially serology, are widely available and relatively sensitive, their specificity is low. Guidelines indicated that no single test can be considered as the gold standard for the diagnosis of H. pylori infection and that one should consider the method's advantages and disadvantages. Based on four epidemiological studies, culture and RUT present a sensitivity of 74.2-90.8% and 83.3-86.9% and a specificity of 97.7-98.8% and 95.1-97.2%, respectively, when using IHC as a gold standard. The sensitivity of serology is quite high, but that of the urine test was lower compared with that of the other methods. Thus, indirect test validation is important although some commercial kits propose universal cut-off values.
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Project description:The persuasiveness of genomic evidence has pressured scientific agencies to supplement or replace well-established methodologies to inform public health and food safety decision-making. This study of 52 epidemiologically defined Listeria monocytogenes isolates, collected between 1981 and 2011, including nine outbreaks, was undertaken (1) to characterize their phylogenetic relationship at finished genome-level resolution, (2) to elucidate the underlying genetic diversity within an endemic subtype, CC8, and (3) to re-evaluate the genetic relationship and epidemiology of a CC8-delimited outbreak in Canada in 2008. Genomes representing Canadian Listeria outbreaks between 1981 and 2010 were closed and manually annotated. Single nucleotide variants (SNVs) and horizontally acquired traits were used to generate phylogenomic models. Phylogenomic relationships were congruent with classical subtyping and epidemiology, except for CC8 outbreaks, wherein the distribution of SNV and prophages revealed multiple co-evolving lineages. Chronophyletic reconstruction of CC8 evolution indicates that prophage-related genetic changes among CC8 strains manifest as PFGE subtype reversions, obscuring the relationship between CC8 isolates, and complicating the public health interpretation of subtyping data, even at maximum genome resolution. The size of the shared genome interrogated did not change the genetic relationship measured between highly related isolates near the tips of the phylogenetic tree, illustrating the robustness of these approaches for routine public health applications where the focus is recent ancestry. The possibility exists for temporally and epidemiologically distinct events to appear related even at maximum genome resolution, highlighting the continued importance of epidemiological evidence.
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Project description:Collectively, the completion of the Human Genome Project and subsequent development of high-throughput next-generation sequencing methodologies have revolutionized genomic research. However, the rapid sequencing and analysis of thousands upon thousands of human exomes and genomes has taught us that most genes, including those known to cause heritable cardiovascular disorders such as long QT syndrome, harbor an unexpected background rate of rare, and presumably innocuous, non-synonymous genetic variation. In this Review, we aim to reappraise the genetic architecture underlying both the acquired and congenital forms of long QT syndrome by examining how the clinical phenotype associated with and background genetic variation in long QT syndrome-susceptibility genes impacts the clinical validity of existing gene-disease associations and the variant classification and reporting strategies that serve as the foundation for diagnostic long QT syndrome genetic testing.
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Project description:Studies on familial aggregation of cancer may suggest an overall contribution of inherited genes or a shared environment in the development of malignant disease. We performed a meta-analysis on familial clustering of prostate cancer. Out of 74 studies reporting data on familial aggregation of prostate cancer in unselected populations retrieved by a Pubmed search and browsing references, 33 independent studies meeting the inclusion criteria were used in the analysis performed with the random effects model. The pooled rate ratio (RR) for first-degree family history, i.e. affected father or brother, is 2.48 (95% confidence interval: 2.25-2.74). The incidence rate for men who have a brother who got prostate cancer increases 3.14 times (CI:2.37-4.15), and for those with affected father 2.35 times (CI:2.02-2.72). The pooled estimate of RR for two or more affected first-degree family members relative to no history in father and in brother is 4.39 (CI:2.61-7.39). First-degree family history appears to increase the incidence rate of prostate cancer more in men under 65 (RR:2.87, CI:2.21-3.74), than in men aged 65 and older (RR:1.92, CI:1.49-2.47), p for interaction?=?0.002. The attributable fraction among those having an affected first-degree relative equals to 59.7% (CI:55.6-63.5%) for men at all ages, 65.2% (CI:57.7-71.4%) for men younger than 65 and 47.9% (CI:37.1-56.8%) for men aged 65 or older. For those with a family history in 2 or more first-degree family members 77.2% (CI:65.4-85.0%) of prostate cancer incidence can be attributed to the familial clustering. Our combined estimates show strong familial clustering and a significant effect-modification by age meaning that familial aggregation was associated with earlier disease onset (before age 65).
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Project description:BackgroundMany individuals who survive tuberculosis disease face ongoing disability and elevated mortality risks. However, the impact of post-tuberculosis sequelae is generally omitted from policy analyses and disease burden estimates. We therefore estimated the global burden of tuberculosis, inclusive of post-tuberculosis morbidity and mortality.MethodsWe constructed a hypothetical cohort of individuals developing tuberculosis in 2019, including pulmonary and extrapulmonary disease. We simulated lifetime health outcomes for this cohort, stratified by country, age, sex, HIV status, and treatment status. We used disability-adjusted life-years (DALYs) to summarise fatal and non-fatal health losses attributable to tuberculosis, during the disease episode and afterwards. We estimated post-tuberculosis mortality and morbidity based on the decreased lung function caused by pulmonary tuberculosis disease.FindingsGlobally, we estimated 122 (95% uncertainty interval [UI] 98-151) million DALYs due to incident tuberculosis disease in 2019, with 58 (38-83) million DALYs attributed to post-tuberculosis sequelae, representing 47% (95% UI 37-57) of the total burden estimate. The increase in burden from post-tuberculosis varied substantially across countries and regions, driven largely by differences in estimated case fatality for the disease episode. We estimated 12·1 DALYs (95% UI 10·0-14·9) per incident tuberculosis case, of which 6·3 DALYs (5·6-7·0) were from the disease episode and 5·8 DALYs (3·8-8·3) were from post-tuberculosis. Per-case post-tuberculosis burden estimates were greater for younger individuals, and in countries with high incidence rates. The burden of post-tuberculosis was spread over the remaining lifetime of tuberculosis survivors, with almost a third of total DALYs (28%, 95% UI 23-34) accruing 15 or more years after incident tuberculosis.InterpretationPost-tuberculosis sequelae add substantially to the overall disease burden caused by tuberculosis. This hitherto unquantified burden has been omitted from most previous policy analyses. Future policy analyses and burden estimates should take better account of post-tuberculosis, to avoid the potential misallocation of funding, political attention, and research effort resulting from continued neglect of this issue.FundingNational Institutes of Health.
| S-EPMC8609280 | biostudies-literature
Project description:Background: Metabolic and physicochemical evaluation is recommended to manage the condition of patients with nephrolithiasis. The estimation of the saturation state (β values) is often included in the diagnostic work-up, and it is preferably performed through calculations. The free concentrations of constituent ions are estimated by considering the main ionic soluble complexes. It is contended that this approach is liable to an overestimation of β values because some complexes may be overlooked. A recent report found that β values could be significantly lowered upon the addition of new and so far neglected complexes, [Ca(PO4)Cit]4- and [Ca2H2(PO4)2]. The aim of this work was to assess whether these complexes can be relevant to explaining the chemistry of urine. Methods: The Ca-phosphate-citrate aqueous system was investigated by potentiometric titrations. The stability constants of the parent binary complexes [Cacit]- and [CaPO4]-, and the coordination tendency of PO43- toward [Ca(cit)]- to form the ternary complex, were estimated. βCaOx and βCaHPO4 were then calculated on 5 natural urines by chemical models, including or not including the [CaPO4]- and [Ca(PO4)cit]4- species. Results: Species distribution diagrams show that the [Ca(PO4)cit]4- species was only noticeable at pH > 8.5 and below 10% of the total calcium. β values estimated on natural urine were slightly lowered by the formation of [CaPO4]- species, whereas [Ca(PO4)cit]4- results were irrelevant. Conclusions: While [CaPO4]- species have an impact on saturation levels at higher pHs, the existence of ternary complex and of the dimer is rejected.
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Project description:The discovery of the multiple roles of mitochondria-endoplasmic reticulum (ER) juxtaposition in cell biology often relied upon the exploitation of Mitofusin (Mfn) 2 as an ER-mitochondria tether. However, this established Mfn2 function was recently questioned, calling for a critical re-evaluation of Mfn2's role in ER-mitochondria cross-talk. Electron microscopy and fluorescence-based probes of organelle proximity confirmed that ER-mitochondria juxtaposition was reduced by constitutive or acute Mfn2 deletion. Functionally, mitochondrial uptake of Ca2+ released from the ER was reduced following acute Mfn2 ablation, as well as in Mfn2-/- cells overexpressing the mitochondrial calcium uniporter. Mitochondrial Ca2+ uptake rate and extent were normal in isolated Mfn2-/- liver mitochondria, consistent with the finding that acute or chronic Mfn2 ablation or overexpression did not alter mitochondrial calcium uniporter complex component levels. Hence, Mfn2 stands as a bona fide ER-mitochondria tether whose ablation decreases interorganellar juxtaposition and communication.
| S-EPMC5056088 | biostudies-literature
Project description:Since 2007, genome-wide association (GWA) studies have identified numerous well-supported, novel genetic risk loci for common cancers; however, there are concerns that this technology is reaching its limits. We provide an overview of GWA-identified genetic associations with solid tumors. We simulated the distribution of population risk alleles for colorectal, prostate, testicular, and thyroid cancers based on genetic variants identified in GWA studies. We also evaluated whether statistical power to detect typical genetic effects could be improved with studies performing GWA analyses of all available samples rather than multistage designs. Fifty-six eligible articles yielded 92 eligible associations between cancer phenotypes and genetic variants with a median per-allele odds ratio (OR) of 1.22 (interquartile range = 1.15-1.36). Half of the associations pertained to prostate, colorectal, or breast cancer. Individuals at the upper quartile of simulated risk had only 2.1- to 4.2-fold higher relative risk than those in the lower quartile. Comprehensive evaluation of currently available samples with GWA platforms would yield few additional variants with per-allele OR = 1.4, but many more variants with OR = 1.2 could be detected; statistical power to detect weak associations (OR = 1.07) would still be negligible. The GWA approach is effective in identifying common genetic variants with moderate effect; however, identifying loci with very small effects and rare variants will require major new efforts. At present, the utility of GWA-identified risk loci in risk stratification for cancer is limited.
| S-EPMC2886095 | biostudies-literature
Project description:OBJECTS: Deliberate termination of life of newborns (involuntary euthanasia) with meningomyelocele (MMC) is practiced openly only in The Netherlands. 'Unbearable and hopeless suffering' is the single most cited criterion for this termination, together with the notion that 'there are no other proper medical means to alleviate this suffering'. In this paper, both (and other) statements are questioned, also by putting them in a broader perspective. METHODS: First, a historical overview of the treatment of newborns with MMC is presented, concentrating on the question of selection for treatment. Second, a thorough analysis is made of the criteria used for life termination. Third, a case of a newborn with a very severe MMC is presented as a 'reference case'. CONCLUSION: 'Unbearable and hopeless suffering' cannot be applied to newborns with MMC. They are not 'terminally ill' and do have 'prospects of a future'. In these end-of-life decisions, 'quality of life judgments' should not be applied. When such a newborn is not treated, modern palliative care always will suffice in eliminating possible discomfort. There is no reason whatsoever for active life-termination of these newborns.
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