Abdominal Tuberculosis in Adult: 10-Year Experience in a Teaching Hospital in Central Taiwan

Background/PurposeTuberculosis (TB) is an important communicable disease worldwide. The clinical presentation of abdominal TB often mimics various gastrointestinal disorders and may delay accurate diagnosis. In this study, we conducted a 10-year retrospective study to investigate the clinical manifestations, treatment responses and outcomes of abdominal TB.MethodsThis retrospective study recruited patients presenting between January 1998 and December 2007; all patients ≥ 18 years of age with a diagnosis of abdominal TB were enrolled. Patient charts were thoroughly reviewed and clinical specimens were processed in the laboratory using the BBL MycoPrep System and BACTEC MGIT 960 Mycobacterial Detection System. Mycobacterium tuberculosis complex was confirmed by acid fast stain and the BD ProbeTec ET System.ResultsDuring the study period, 34 patients were diagnosed with abdominal TB. The mean age was 55+18 years. Fourteen patients (41%) had no risk factors; however, 20 patients (59%) had at least one risk factor. Abdominal pain (94.1%), abdominal fullness (91.2%), anorexia (88.2%) and ascites (76.5%) were the most common presenting symptoms. The peritoneum (88%) was the most commonly involved site. Patients with risk factors such as liver cirrhosis, end-stage renal disease and diabetes mellitus had a higher positive rate of acid-fast stain and mycobacterial culture from abdominal specimens (p = 0.02 and 0.05, respectively). The crude mortality rate was 9% and the attributed mortality rate was 3%.ConclusionIn an endemic area like Taiwan, regardless of whether a patient has risk factors for TB, abdominal TB should be seriously considered as a differential diagnosis when a patient presents with gastrointestinal symptoms and unexplained ascites

Dual Supramolecular Nanoparticle Vectors Enable CRISPR/Cas9-Mediated Knockin of Retinoschisin 1 Gene-A Potential Nonviral Therapeutic Solution for X-Linked Juvenile Retinoschisis.

The homology-independent targeted integration (HITI) strategy enables effective CRISPR/Cas9-mediated knockin of therapeutic genes in nondividing cells in vivo, promising general therapeutic solutions for treating genetic diseases like X-linked juvenile retinoschisis. Herein, supramolecular nanoparticle (SMNP) vectors are used for codelivery of two DNA plasmids-CRISPR-Cas9 genome-editing system and a therapeutic gene, Retinoschisin 1 (RS1)-enabling clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) knockin of the RS1 gene with HITI. Through small-scale combinatorial screenings, two SMNP vectors, with Cas9 and single guide RNA (sgRNA)-plasmid in one and Donor-RS1 and green fluorescent protein (GFP)-plasmid in the other, with optimal delivery performances are identified. These SMNP vectors are then employed for CRISPR/Cas9 knockin of RS1/GFP genes into the mouse Rosa26 safe-harbor site in vitro and in vivo. The in vivo study involves intravitreally injecting the two SMNP vectors into the mouse eyes, followed by repeated ocular imaging by fundus camera and optical coherence tomography, and pathological and molecular analyses of the harvested retina tissues. Mice ocular organs retain their anatomical integrity, a single-copy 3.0-kb RS1/GFP gene is precisely integrated into the Rosa26 site in the retinas, and the integrated RS1/GFP gene is expressed in the retinas, demonstrating CRISPR/Cas9 knockin of RS1/GFP gene

Genome-Wide Association Study of Young-Onset Hypertension in the Han Chinese Population of Taiwan

Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the results at the first stage based on a total of 1,008 patients and 1,008 controls. Single-locus association tests, multilocus association tests and pair-wise gene-gene interaction tests were performed to identify young-onset hypertension susceptibility genes. After considering stringent adjustments of multiple testing, gene annotation and single-nucleotide polymorphism (SNP) quality, four SNPs from two SNP triplets with strong association signals (−log10(p)>7) and 13 SNPs from 8 interactive SNP pairs with strong interactive signals (−log10(p)>8) were carefully re-examined. The confirmatory study verified the association for a SNP quartet 219 kb and 495 kb downstream of LOC344371 (a hypothetical gene) and RASGRP3 on chromosome 2p22.3, respectively. The latter has been implicated in the abnormal vascular responsiveness to endothelin-1 and angiotensin II in diabetic-hypertensive rats. Intrinsic synergy involving IMPG1 on chromosome 6q14.2-q15 was also verified. IMPG1 encodes interphotoreceptor matrix proteoglycan 1 which has cation binding capacity. The genes are novel hypertension targets identified in this first genome-wide hypertension association study of the Han Chinese population

Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as Hypertension Susceptibility Genes in Han Chinese with a Genome-Wide Gene-Based Association Study

Hypertension is a complex disorder with high prevalence rates all over the world. We conducted the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide single-nucleotide-polymorphism data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes for hypertension were identified and also validated with permutation tests. Seventeen of the 100 genes exhibited differential allelic and expression distributions between patient and control groups. These genes provided a good molecular signature for classifying hypertensive patients and normotensive controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only identified by our gene-based association scan and gene expression analysis but were also replicated by a gene-based association analysis of the Hong Kong Hypertension Study. Moreover, cis-acting expression quantitative trait loci associated with the differentially expressed genes were found and linked to hypertension. IGF1, which encodes insulin-like growth factor 1, is associated with cardiovascular disorders, metabolic syndrome, decreased body weight/size, and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain-containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1, which encodes the scm-like with four MBT domains protein 1, is a novel hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant differential allelic and expressed distributions between hypertensive patients and normotensive controls. GRB14 was also found relevant to blood pressure in a previous genetic association study in East Asian populations. TMEM56 and KIAA1797 may be specific to Taiwanese populations, because they were not validated by the two replication studies. Identification of these genes enriches the collection of hypertension susceptibility genes, thereby shedding light on the etiology of hypertension in Han Chinese populations

Association between acute aortic dissection and the distribution of aortic calcification.

ObjectiveAortic calcification (AC) is associated with increased risks of cardiovascular events and mortality. Numerous studies have explored the association between calcification and abdominal artery aneurysm. However, evidence regarding the association between AC and acute aortic dissection (AAD) is limited. We aimed to evaluate the association between AC-related variables and the development of intimal tear (IT) in patients with AAD.MethodsWe conducted a retrospective observational study involving 64 patients with type A AAD and 32 patients with type B AAD from February, 2011 to January, 2017 at a tertiary referral medical center in Taiwan. We used the default analysis module "calcification score analysis" to calculate all the calcification variables, including AC scores and volume.ResultsWe identified an association between AC and AAD. Patients with AAD had a greater AC volume in the aortic arch and greater AC scores for both the ascending aorta and the aortic arch than did patients without AAD. However, hypertension and coronary artery disease, rather than AC remained to be the independent risk factor for AAD in multivariate analysis. Patients with type A AAD had greater mean and cumulative AC volumes in the aortic arch, greater cumulative AC volumes in the whole aorta and higher cumulative AC scores in the aortic arch than did patients with type B AAD. ACs were superimposed on ITs in nearly half of the patients with AAD. In patients with type A AAD, AC was more commonly located distal to the IT and farther from the IT.ConclusionsWe identified the associations between AC-related variables and the location of IT in patients with AAD. However, AC was not an independent risk factor for AAD. The distribution of AC was different between patients with type A and type B AAD

Prediction of Shearing and Ploughing Constants in Milling of Inconel 718

The present study proposes an integrated prediction model for both shearing and ploughing constants for the peripheral milling of Inconel 718 by using a preidentified mean normal friction coefficient. An equation is presented for the identification of normal mean friction angle of oblique cutting in milling. A simplified oblique cutting model is adopted for obtaining the shear strain and shearing constants for a tool of given helix angle, radial rake angle, and honed edge radius. The shearing and ploughing constants predicted from analytical model using the Merchant’s shear angle formula and the shear flow stress from the selected Johnson–Cook material law are shown to be consistent with the experimental results. The experimentally identified normal friction angles and shearing and edge ploughing constants for the Inconel 718 milling process are demonstrated to have approximately constant values irrespective of the average chip thickness. Moreover, the predicted forces obtained in milling aged Inconel 718 alloy are in good agreement with the experimental force measurements reported in the literature. Without considering the thermal–mechanical coupling effect in the material law, the presented model is demonstrated to work well for milling of both annealed and aged Inconel 718

Cognitive MRI-TRUS fusion-targeted prostate biopsy according to PI-RADS classification in patients with prior negative systematic biopsy results

Background: The purpose of this study was to evaluate the prostate cancer yield rate of targeted transrectal ultrasound (TRUS)-guided biopsy with cognitive magnetic resonance imaging (MRI) registration without concurrent systematic biopsy in patients with previous negative systematic TRUS-guided biopsy results and persistently elevated prostate-specific antigen (PSA) levels. Methods: In this prospective study conducted from August 2013 to January 2015, patients with at least one previous negative systematic TRUS-guided biopsy and persistently high PSA (≥4 ng/mL) levels were referred for multiparametric MRI (mpMRI). Those patients with suspicious findings on mpMRI received a subsequent cognitive MRI-TRUS fusion biopsy. The cancer-detection rate, tumor location, and Gleason score were confirmed, and PSA-related data were compared between cancer-yield and noncancer-yield groups. Results: In total, 48 patients were included in this study. MRI was designated to be four and five in 17 patients. Fifteen patients received a cognitive fusion-targeted biopsy, and prostate cancers were detected in 10 patients. The cancer-detection rate was 20.8% (10/48), and the positive-predictive value of MRI was 66.7%. No significant differences were observed in the PSA level, PSA velocity, or transitional zone volume between the cancer-yield and noncancer-yield groups; however, the corresponding difference in PSA transitional zone density was significant (p=0.025). Conclusion: Cognitive MRI-TRUS fusion-targeted biopsy without concurrent systematic biopsy can detect significant prostate cancer in patients with previous negative systematic biopsy results and persistently elevated PSA levels. Noncancer-yield patients should undergo active surveillance and further follow-ups

Comparison of arthroplasty vs. osteosynthesis for displaced femoral neck fractures: a meta-analysis

Abstract Background This meta-analysis compared clinical outcomes of arthroplasty vs. osteosynthesis for displaced femoral neck fractures. Methods Meta-analysis was performed on the difference in revision rate and overall mortality between participants undergoing osteosynthesis vs. total hip arthroplasty (THA), osteosynthesis vs. hemiarthroplasty (HA), or THA vs. HA. Results Pooled direct and indirect results indicated no significant difference in mortality between THA and HA (pooled OR = 0.87, 95% CI 0.55 to 1.38; P = 0.556), between THA and osteosynthesis (pooled OR = 1.17, 95% CI 0.69 to 1.99; P = 0.553), and between HA and osteosynthesis (pooled OR = 1.21, 95% CI 0.84 to 1.74; P = 0.304). Pooled direct and indirect results indicated no significant difference in revision rates between THA and HA (pooled OR = 0.90, 95% CI 0.26 to 3.19; P = 0.874). But, fewer revisions (OR = 0.19, 95% CI 0.10 to 0.34; P = 0.000) were seen in patients treated with THA than osteosynthesis and also in those treated with HA than osteosynthesis (OR = 0.12, 95% CI 0.07 to 0.20; P = 0.000). After excluding studies without showing normal cognition in inclusion criteria, pooled direct and indirect results also indicated no significant difference in mortality between THA, HA, and osteosynthesis. Similarly, there was no significant difference in revision rates between THA and HA, but HA and THA had significantly lower revision rates compared with osteosynthesis. Conclusions There was no significant difference in overall mortality among osteosynthesis, HA, and THA. However, HA and THA had significantly lower revision rates compared with osteosynthesis. Results of the present study provide support for the use of hip arthroplasty to treat displaced fractures of the femoral neck