Background: and Purpose The association between hemoglobin A1c (HbA1c) and stroke risk along with its subtypes is rarely reported. We aimed to investigate the association between HbA1c and the risk of incident stroke in patients with type 2 diabetes based on real world data from three healthcare systems. Methods: We performed a retrospective cohort study of 27,113 African Americans and 40,431 whites with type 2 diabetes. Demographic, anthropometric, laboratory, and medication information were abstracted from the National Patient-Centered Clinical Research Network common data model. Incident stroke events including both ischemic and hemorrhagic stroke were defined. Results: During a mean follow-up period of 3.79±1.68 years, 7,735 patients developed stroke (6,862 ischemic and 873 hemorrhagic). Multivariable-adjusted hazard ratios across levels of HbA1c at baseline (<6.0%, 6.0% to 6.9% [reference group], 7.0% to 7.9%, 8.0% to 8.9%, 9.0% to 9.9%, and ≥10%) were 1.07, 1.00, 1.13, 1.23, 1.27, and 1.37 (Ptrend <0.001) for total stroke, 1.02, 1.00, 1.13, 1.20, 1.24, and 1.35 (Ptrend <0.001) for ischemic stroke, and 1.40, 1.00, 1.14, 1.47, 1.47, and 1.51 (Ptrend=0.002) for hemorrhagic stroke. When we used an updated mean value of HbA1c, the U-shaped association of HbA1c with stroke risk did not change. This U-shaped association was consistent among patients of different subgroups. The U-shaped association was more pronounced among patients taking antidiabetic, lipid-lowering, and antihypertensive medications compared with those without these medications. Conclusions These data suggest that diabetes management may have to be individualized according to the guideline recommendations rather than intensively attempting to lower HbA1c.

Accurate detection of homologous recombination deficiency (HRD) in cancer patients is paramount in clinical applications, as HRD confers sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. With the advances in genome sequencing technology, mutational profiling on a genome-wide scale has become readily accessible, and our knowledge of the genomic consequences of HRD has been greatly expanded and refined. Here, we review the recent advances in HRD detection methods. We examine the copy number and structural alterations that often accompany the genome instability that results from HRD, describe the advantages of mutational signature-based methods that do not rely on specific gene mutations, and review some of the existing algorithms used for HRD detection. We also discuss the choice of sequencing platforms (panel, exome, or whole-genome) and catalog the HRD detection assays used in key PARP inhibitor trials.

Accurate detection of homologous recombination deficiency (HRD) in cancer patients is paramount in clinical applications, as HRD confers sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. With the advances in genome sequencing technology, mutational profiling on a genome-wide scale has become readily accessible, and our knowledge of the genomic consequences of HRD has been greatly expanded and refined. Here, we review the recent advances in HRD detection methods. We examine the copy number and structural alterations that often accompany the genome instability that results from HRD, describe the advantages of mutational signature-based methods that do not rely on specific gene mutations, and review some of the existing algorithms used for HRD detection. We also discuss the choice of sequencing platforms (panel, exome, or whole-genome) and catalog the HRD detection assays used in key PARP inhibitor trials.

Accurate detection of homologous recombination deficiency (HRD) in cancer patients is paramount in clinical applications, as HRD confers sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. With the advances in genome sequencing technology, mutational profiling on a genome-wide scale has become readily accessible, and our knowledge of the genomic consequences of HRD has been greatly expanded and refined. Here, we review the recent advances in HRD detection methods. We examine the copy number and structural alterations that often accompany the genome instability that results from HRD, describe the advantages of mutational signature-based methods that do not rely on specific gene mutations, and review some of the existing algorithms used for HRD detection. We also discuss the choice of sequencing platforms (panel, exome, or whole-genome) and catalog the HRD detection assays used in key PARP inhibitor trials.

Accurate detection of homologous recombination deficiency (HRD) in cancer patients is paramount in clinical applications, as HRD confers sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. With the advances in genome sequencing technology, mutational profiling on a genome-wide scale has become readily accessible, and our knowledge of the genomic consequences of HRD has been greatly expanded and refined. Here, we review the recent advances in HRD detection methods. We examine the copy number and structural alterations that often accompany the genome instability that results from HRD, describe the advantages of mutational signature-based methods that do not rely on specific gene mutations, and review some of the existing algorithms used for HRD detection. We also discuss the choice of sequencing platforms (panel, exome, or whole-genome) and catalog the HRD detection assays used in key PARP inhibitor trials.

DNA barcoding is a powerful approach for characterizing species of organisms, especially those with almost identical morphological features, thereby helping to to establish phylogenetic relationships and reveal evolutionary histories. In this study, we chose a 648-bp segment of the mitochondrial gene, cytochrome c oxidase subunit 1 (COI), as a standard barcode region to establish phylogenetic relationships among brine shrimp (Artemia) species from major habitats around the world and further focused on the biodiversity of Artemia species in China, especially in the Tibetan Plateau. Samples from five major salt lakes of the Tibetan Plateau located at altitudes over 4,000 m showed clear differences from other Artemia populations in China. We also observed two consistent amino acid changes, 153A/V and 183L/F, in the COI gene between the high and low altitude species in China. Moreover, indels in the COI sequence were identified in cyst and adult samples unique to the Co Qen population from the Tibetan Plateau, demonstrating the need for additional investigations of the mitochondrial genome among Tibetan Artemia populations.
Animals ; Artemia ; classification ; genetics ; Base Sequence ; China ; DNA, Mitochondrial ; chemistry ; genetics ; Electron Transport Complex IV ; genetics ; Genetic Variation ; Molecular Sequence Data ; Phylogeny ; Selection, Genetic ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; Tibet

To validate the use of the Index of Complexity, Outcome and Need (ICON) in assessing orthodontic treatment need among 12-13 year-olds in southern China, we determined the threshold value of ICON based on Chinese orthodontists' judgments. The samples consisted of 335 students in grade 7 from 16 randomly selected middle schools in Chengdu, China. Three associate professors provided ICON scores for each participant and the results were compared with the gold standard judgments from 25 experts on treatment needs. Based on the gold standard, 195 casts belonged to the treatment category, while the rest 140 belonged to the no-treatment category. With the international cutoff point of 43, the sensitivity and specificity of the ICON score were 0.29 and 0.98.The best compromise between sensitivity and specificity in Chengdu, compared with the gold standard, was found at a cutoff point of 29, and the sensitivity and specificity were 0.88 and 0.83. When used to evaluate the treatment need of 12-13 year-olds in southern China, the international ICON cutoff value did not correspond well with Chinese orthodontists' judgments; a lower cutoff value of 29 offered a greater sensitivity and specificity with respect to expert orthodontists' perception of treatment need.
Adolescent ; Child ; China ; epidemiology ; Cross-Cultural Comparison ; Data Collection ; Dental Health Surveys ; methods ; standards ; Female ; Health Services Needs and Demand ; statistics & numerical data ; Humans ; Male ; Malocclusion ; diagnosis ; epidemiology ; Needs Assessment ; statistics & numerical data ; Observer Variation ; Orthodontics, Corrective ; standards ; statistics & numerical data ; Reference Values ; Reproducibility of Results ; Sensitivity and Specificity

Atopic dermatitis (AD) is among the most common skin disorders in humans. Although a variety of regimens are available for the treatment of AD, preventive approaches are limited. Recent studies have demonstrated that certain naturally-occurring herbal medicines are effective in preventing the development of AD via divergent mechanisms, such as inhibiting cytokine and chemokine expression, IgE production, inflammatory cell infiltration, histamine release, and/or enhancement of epidermal permeability barrier function. Yet, they exhibit few adverse effects. Since herbal medicines are widely available, inexpensive and generally safe, they could represent an ideal approach for preventing the development of AD, in both highly developed and developing countries.
Animals ; Chemokines ; metabolism ; Dermatitis, Atopic ; prevention & control ; Disease Models, Animal ; Herbal Medicine ; Humans ; Immunoglobulin E ; metabolism ; Inflammation ; pathology

Objective To investigate the blood pressure change in relation to the evolution of impaired glucose tolerance (IGT). Methods From 1986 to 1992, 334 subjects with IGT were randomized to placebo, diet, exercise and diet plus exercise intervention groups. No anti-hypertension drug was given to these enrolled subjects. Blood pressure was measured at the beginning and the end of the six-year prospective study. In this analysis these subjects were stratified to seven subgroups based on 2 h plasma glucose (2hPG) level during OGTT at the end of the study: < 7.8,7.8~8.8,8.9~9.9,10.0~11.0,11.1~13.8,13.9~16.6 and≥16.7mmol/L. Blood pressure changes in relation to the evolution of glucose tolerance in these subgroups were compared by least square mean procedure. Results Changes of systolic blood pressure (SBP) in average in these seven groups were -2.4,0.6,7.7,4.3,1.7,-2.9and-6.9mm Hg (1mm Hg=0.133kPa), and changes of diastolic blood pressure (DBP) were-3.2,3.0,3.3,1.7,-0.7,-1.3 and-3.7mm Hg respectively after controlling for age, sex, BMI at baseline and Δ BMI during the follow-up period. In those subjects with IGT evolved into normal glucose tolerance (NGT) or diabetes, reductions in SBP and DBP were significantly greater than those who retained IGT with 2hPG between 8.9-9.9mmol/L (all P < 0.05 ). In 264 out of the 334 subjects with IGT and blood pressure≥130/80mm Hg at baseline, blood pressure changed more strikingly: changes of SBP in these groups were-5.2,-2.6,5.2,2.3,-2.3,-4.2,-7.6mm Hg, and DBP were -5.0, -3.7,1.5, -2.9, -4.3, - 4.0 and-6.0mm Hg respectively after the adjustment of age, sex, BMI, BMI variation. The reductions of SBP and DBP in subjects whose status of IGT was converted to NGT or diabetes were significantly greater than those with retained IGT and 2hPG between 8.9-9.9mmol/L. Conclusion Blood pressure is increased in the subjects with IGT who retained in the IGT group during the six-year follow-up period in Da-Qing Study. On the contrary, subjects with IGT evolved into NGT or diabetes demonstrate significant reduction of blood pressure.

Non-small cell lung cancer is recognized as the deadliest cancer across the globe. In some areas, it is more common in women than even breast and cervical cancer. Its rise, vaulted by smoking habits and increasing air pollution, has garnered much attention and resource in the medical field. The first lung cancer treatments were developed more than half a century ago. Unfortunately, many of the earlier chemotherapies often did more harm than good, especially when they were used to treat genetically unsuitable patients. With the introduction of personalized medicine, physicians are increasingly aware of when, how, and in whom, to use certain anti-cancer agents. Drugs such as tyrosine kinase inhibitors, anaplastic lymphoma kinase inhibitors, and monoclonal antibodies possess limited utility because they target specific oncogenic mutations, but other drugs that target mechanisms universal to all cancers do not. In this review, we discuss many of these non-oncogene-targeting anti-cancer agents including DNA replication inhibitors (