The high rate of neuropsychologic sequelae in CM survivors indicates that initial antifungal therapy is far from being satisfactory. This prospective cross-sectional study applied DTI on HIV-negative ...CM patients to determine whether microstructural changes in brain tissue are associated with subsequent cognitive symptoms.
Fifteen patients with HIV-negative CM and 15 sex- and age-matched healthy volunteers were evaluated and compared. All underwent complete medical and neurologic examinations and neuropsychologic testing. Brain DTI was obtained to derive the FA and ADC of several brain regions. Correlations among DTI parameters, neuropsychologic rating scores, and cryptococcal-antigen titer in CSF were analyzed.
Significant ADC values increased and FA values decreased in HIV-negative CM patients in multiple selected regions of interest, including the genus of the corpus callosum and the frontal, parietal, orbito-frontal, and periventricular white matter and lentiform nucleus. Higher CSF cryptococcal-antigen titer on admission was associated with poorer DTI parameters (r = -0.666, P = .018), which were linearly related to worse cognitive performance during follow-up.
The decline in brain DTI parameters in the associated brain areas indicates an HIV-negative CM microstructural pathology that is related to neuropsychologic consequences.
Metabolic syndrome (MS) was conceptualized to identify people at risk for cardiovascular disease and type 2 diabetes; however, the epidemiology of MS and its combinations of components in older ...adults remains unclear. Data from the Senior Health Examination Program of the New Taipei City Government in Taiwan in 2014 were obtained for this study. All participants aged 65 years or older and those with a prior history of cardiovascular disease, cerebrovascular disease, or diabetes mellitus were excluded. 29,164 senior citizens were retrieved for this study, and 12,331 (41.28%) of the participants were male. Female participants were more likely to have MS (42.7% vs.31.3%, p <0.001). Female participants with MS were older than those without MS (73.15±6.5 vs. 72.10±6.14 years, p <0.001). Conversely, male participants with MS were younger than those without MS (72.93±6.70 vs. 73.52±6.98 years, p <0.001). The most common combination of MS components was the triad of high blood glucose, high blood pressure and central obesity (25.2% of all participants with MS). Age-related changes in MS component combinations were noted only when central obesity was present. The strongest MS component combination for new-onset diabetes mellitus was high blood glucose, hypertriglyceridemia, reduced HDL-C and central obesity (HR: 5.42, P<0.001). In conclusion, not all component combinations of MS were of the same prognostic impact or the risk for new-onset diabetes mellitus. Further study is needed to develop individualized intervention programs for MS based on risk profiles of older adults is needed.
Background
Whether there is a difference in survival after neoadjuvant chemoradiotherapy plus surgery (CRT‐S) compared with definitive chemoradiotherapy (dCRT) in patients with locally advanced ...oesophageal squamous cell carcinoma (SCC) remains controversial.
Methods
Patients with SCC who underwent curative treatment from 2008 to 2014 were identified from the Taiwan Cancer Registry. Propensity score matching was undertaken to balance pretreatment clinical variables. Overall survival was compared between patients undergoing CRT‐S or dCRT. Univariable and multivariable analyses were performed to identify prognostic factors for overall survival.
Results
A total of 5832 patients with clinical stage II and III oesophageal SCC receiving CRT‐S (1754) or dCRT (4078) were included. After propensity score matching, each group included 1661 patients. The 3‐year overall survival rate for patients treated with CRT‐S was 41·1 per cent compared with 17·9 per cent for those who had dCRT (P < 0·001). In multivariable analysis, treatment modality was an independent prognostic factor in the overall cohort before propensity score matching: hazard ratio 0·45 (95 per cent c.i. 0·40 to 0·51) for CRT‐S versus dCRT (P < 0·001). In separate analyses of patients with clinical stage II and those with stage III disease, CRT‐S was associated with significantly better overall survival than dCRT.
Conclusion
Neoadjuvant chemoradiotherapy and oesophagectomy is associated with better overall survival than dCRT in patients with stage II and III oesophageal SCC.
Surgery indicated after chemoradiation
Please cite this paper as: Lee C, Lin S, Lin C, Shih J, Lin T, Su Y. Clinical utility of array comparative genomic hybridisation for prenatal diagnosis: a cohort study of 3171 pregnancies. BJOG ...2012;119:614–625.
Objective To evaluate the clinical value of prenatal array comparative genomic hybridisation (CGH) in screening for submicroscopic genomic imbalances.
Design Cross‐sectional study.
Setting Tertiary referral centre.
Population From June 2008 to February 2011, 3171 fetuses underwent prenatal array CGH testing and karyotyping at the National Taiwan University Hospital. Indications for invasive prenatal diagnosis included abnormal karyotype, abnormal ultrasound, advanced maternal age and parental anxiety.
Methods In all, 2497 fetuses were screened with 1‐Mb resolution bacterial artificial chromosome array‐based CGH, and 674 fetuses with 60‐K oligonucleotide array‐based CGH. Multiplex ligation‐dependent probe amplification, fluorescence in situ hybridization, or 105‐K oligonucleotide array CGH provided further confirmation.
Main outcome measure Copy number variations identified by array CGH.
Results Array CGH detected numerical chromosome anomalies in 37 (1.2%) fetuses, microdeletion/duplication in 34 (1.1%) fetuses, large deletion/duplication in 13 (0.4%) fetuses, benign copy number changes in 13 (0.4%) fetuses and variation of unknown clinical significance in five (0.2%) fetuses. Array CGH was effective in identifying submicroscopic genomic imbalance in fetuses with de novo balance translocations (2/17, 1.8%), supernumerary marker chromosomes (3/6, 50%), and abnormal prenatal ultrasound findings (33/194, 17.0%). Array CGH detected microdeletions/duplications in 12 fetuses with normal karyotype.
Conclusion Prenatal array CGH is effective in screening for submicroscopic genomic imbalance. Array CGH may add 8.2% to the diagnostic field, compared with conventional karyotyping, for fetuses with abnormal ultrasound results, and is particularly useful in fetuses with karyotypic balanced translocation or marker chromosomes. There is a 0.52% baseline risk of submicroscopic genomic imbalance, even in women with an uneventful prenatal examination.
Objective
Recent reports have identified hypercholesterolaemia as a significant risk factor for idiopathic sudden sensorineural hearing loss (ISSNHL). Therefore, we investigated whether lipid ...profiles and lipoprotein ratios are correlated with the prognosis of hearing recovery in ISSNHL patients.
Design
A retrospective cohort study.
Main outcome measures
Patients with ISSNHL were classified into four groups (complete, partial, slight and no recovery) according to their degree of hearing recovery using Siegel's criteria and the Sudden Deafness Research Group (SDRG) criteria developed by the Japanese Ministry of Welfare. All patients' lipid profiles were analysed, including total cholesterol (TC), high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) cholesterol and triglycerides. We calculated the ratios of TC/HDL‐C and LDL‐C/HDL‐C and used statistical methods to evaluate correlations between lipid profiles and lipoprotein ratios and ISSNHL prognosis.
Results
Hearing recovery was observed in 103 (62.0%) of 166 cases using Siegel's criteria and in 114 (68.7%) of 166 cases using SDRG's criteria. Among the three recovery groups (i.e. excluding the no recovery group), the ratio of LDL‐C/HDL‐C was found to be associated with recovery outcome by showing the ratio on an upward trend from complete recovery to slight recovery group, and the difference is statistically significant (P = 0.016 by Siegel's criteria, P = 0.041 by SDRG's criteria). Multiple linear regression analysis further revealed a significantly higher LDL‐C/HDL‐C ratio in slight hearing recovery group compared with complete recovery group (P = 0.007 by Siegel's criteria, P = 0.031 by SDRG's criteria).
Conclusion
We suggested that lipoprotein ratio of LDL‐C/HDL‐C may be a prognostic factor for hearing recovery in ISSNHL patients. Further studies should be conducted to determine whether hearing outcomes in ISSNHL can be improved by changing patients' lipid profiles via antilipidemic treatment.
Purpose
Numerous biomarkers of diabetic kidney disease (DKD) are associated with renal prognosis but head-to-head comparisons are lacking. This study aimed to examine the association of soluble tumor ...necrosis factor receptor type 1 (sTNFR1), fibroblast growth factor 21 (FGF-21), endocan, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and renal outcomes of patients with or without clinical signs of DKD.
Methods
A total of 312 patients were enrolled in a prospective observational study that excluded individuals with estimated glomerular filtration rates (eGFR) < 30 mL/min/1.73 m
2
. Composite renal outcomes included either a > 30% decline in eGFR and worsening albuminuria or both from consecutive tests of blood/urine during a 3.5-year follow-up period.
Results
Higher sTNFR1 and FGF-21, rather than endocan and NT-pro-BNP, levels were associated with renal outcomes but the significance was lost after adjusting for confounders. However, sTNFR1 levels ≥ 9.79 pg/dL or FGF-21 levels ≥ 1.40 pg/dL were associated with renal outcomes after adjusting for the confounders (hazard ration HR 2.76, 95% confidence interval CI 1.36–5.60,
p
= 0.005 for sTNFR1 level; HR 1.95, 95% CI 1.03–3.69,
p
= 0.03 for FGF-21 level). The combination of both levels exhibited even better association with renal outcomes than did either one alone (adjusted HR 4.45, 95% CI 1.86–10.65,
p
= 0.001). The results were consistent among patients with preserved renal function and normoalbuminuria.
Conclusion
Both sTNFR1 and FGF-21 levels were associated with renal outcomes of in patients with type 2 diabetes, and the combination of the abovementioned markers exhibits better predictability.
The association between herpes zoster (HZ) infection and subsequent risk of end stage renal disease (ESRD) in chronic kidney disease (CKD) patients is unknown. We aim to conduct a population-based ...cohort study to investigate the risks of developing ESRD after a HZ attack in CKD patients. From the Taiwan National Health Insurance Research Database, we identified 1,144 CKD patients who had HZ over the period 1997–2008 as HZ cohort. We selected 3,855 age- and sex–matched CKD patients without HZ as comparison cohort. All subjects were followed until the end of 2008 or censored. Cox-proportional hazard regression model was used to estimate the effects of HZ on ESRD risks. A total of 396 patients developed ESRD during the follow-up period, of which 108 subjects were from the HZ cohort and 288 from the comparison cohort. The log–rank test demonstrated that the HZ cohort had significantly higher risk of developing ESRD than the comparison cohort (
P
= 0.0071). The adjusted hazard ratio of subsequent ESRD in the HZ cohort was 1.36 (95 % CI 1.09–1.70) and the hazard ratio increased to 8.71 (95 % CI 5.23–14.5) if the HZ cohort was with concomitant diabetes and hypertension. CKD patients with HZ are at an increased risk of subsequent ESRD. CKD patients with HZ, diabetes, and hypertension have extremely high risk of developing ESRD.
Amelogenesis imperfecta (AI) is a diverse group of inherited diseases featured by various presentations of enamel malformations that are caused by disturbances at different stages of enamel ...formation. While hypoplastic AI suggests a thickness defect of enamel resulting from aberrations during the secretory stage of amelogenesis, hypomaturation AI indicates a deficiency of enamel mineralization and hardness established at the maturation stage. Mutations in ENAM, which encodes the largest enamel matrix protein, enamelin, have been demonstrated to cause generalized or local hypoplastic AI. Here, we characterized 2 AI families with disparate hypoplastic and hypomaturation enamel defects and identified 2 distinct indel mutations at the same location of ENAM, c588+1del and c.588+1dup. Minigene splicing assays demonstrated that they caused frameshifts and truncation of ENAM proteins, p.Asn197Ilefs*81 and p.Asn197Glufs*25, respectively. In situ hybridization of Enam on mouse mandibular incisors confirmed its restricted expression in secretory stage ameloblasts and suggested an indirect pathogenic mechanism underlying hypomaturation AI. In silico analyses indicated that these 2 truncated ENAMs might form amyloid structures and cause protein aggregation with themselves and with wild-type protein through the added aberrant region at their C-termini. Consistently, protein secretion assays demonstrated that the truncated proteins cannot be properly secreted and impede secretion of wild-type ENAM. Moreover, compared to the wild-type, overexpression of the mutant proteins significantly increased endoplasmic reticulum stress and upregulated the expression of unfolded protein response (UPR)–related genes and TNFRSF10B, a UPR-controlled proapoptotic gene. Caspase, terminal deoxynucleotidyl transferase UTP nick-end labeling (TUNEL), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays further revealed that both truncated proteins, especially p.Asn197Ilefs*81, induced cell apoptosis and decreased cell survival, suggesting that the 2 ENAM mutations cause AI through ameloblast cell pathology and death rather than through a simple loss of function. This study demonstrates that an ENAM mutation can lead to generalized hypomaturation enamel defects and suggests proteinopathy as a potential pathogenesis for ENAM-associated AI.
Dysregulation of cell surface proteolysis has been strongly implicated in tumorigenicity and metastasis. In this study, we delineated the role of hepatocyte growth factor activator inhibitor-2 ...(HAI-2) in prostate cancer (PCa) cell migration, invasion, tumorigenicity and metastasis using a human PCa progression model (103E, N1, and N2 cells) and xenograft models. N1 and N2 cells were established through serial intraprostatic propagation of 103E human PCa cells and isolation of the metastatic cells from nearby lymph nodes. The invasion capability of these cells was revealed to gradually increase throughout the serial isolations (103E<N1<N2). In this series of cells, the expression of HAI-2 but not HAI-1 was significantly decreased throughout the progression and occurred in parallel with increased activation of matriptase. The expression level and activity of matriptase increased whereas the HAI-2 protein level decreased over the course of orthotopic tumor growth in mice, which was consistent with the immunohistochemical profiles of matriptase and HAI-2 in archival PCa specimens. Knockdown of matriptase reduced the PCa cell invasion induced by HAI-2 knockdown. HAI-2 overexpression or matriptase silencing in N2 cells downregulated matriptase activity and significantly decreased tumorigenicity and metastatic capability in orthotopically xenografted mice. These results suggest that during the progression of human PCa, matriptase activity is primarily controlled by HAI-2 expression. The imbalance between HAI-2 and matriptase expression led to matriptase activation, thereby increasing cell migration, invasion, tumorigenicity and metastasis.
Airborne disease transmission has always been a topic of wide interests in various fields for decades. Cough is found to be one of the prime sources of airborne diseases as it has high velocity and ...large quantity of droplets. To understand and characterize the flow dynamics of a cough can help to control the airborne disease transmission. This study has measured flow dynamics of coughs with human subjects. The flow rate variation of a cough with time can be represented as a combination of gamma‐probability‐distribution functions. The variables needed to define the gamma‐probability‐distribution functions can be represented by some medical parameters. A robust multiple linear regression analysis indicated that these medical parameters can be obtained from the physiological details of a person. However, the jet direction and mouth opening area during a cough seemed not related to the physiological parameters of the human subjects. Combining the flow characteristics reported in this study with appropriate virus and droplet distribution information, the infectious source strength by coughing can be evaluated.
Practical Implications
There is a clear need for the scientific community to accurately predict and control the transmission of airborne diseases. Transportation of airborne viruses is often predicted using Computational Fluid Dynamics (CFD) simulations. CFD simulations are inexpensive but need accurate source boundary conditions for the precise prediction of disease transmission. Cough is found to be the prime source for generating infectious viruses. The present study was designed to develop an accurate source model to define thermo‐fluid boundary conditions for a cough. The model can aid in accurately predicting the disease transmission in various indoor environments, such as aircraft cabins, office spaces and hospitals.
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