Development Of New Disease Research Articles

Examination and characterization of key factors to seasonal epidemics of downy mildew in native grape species Vitis davidii in southern China with the use of disease warning systems

Spine grape (Vitis davidii) is a major native grape species cultivated in south central China, and the industry is threatened by downy mildew outbreaks caused by Plasmopara viticola in this rainy and warm region. To examine and characterize the local epidemics of this disease in this region, experiments were conducted in Jingzhou in 2012–2013 with variety ‘Gaoshan-2’ and Zhongfang in 2013–2016 with variety ‘Xiangzhenzhu’ in Hunan Province. The number of diseased leaves with new infections (DL_Sum) and disease severity were assessed every 5 days. First, we used a mechanistic simulation model originally developed in Europe to simulate the primary inoculum seasons in these years and found that they ended in early May, suggesting little influences from oospores to the disease in summer. Then we used negative binomial regression to model the temporal changes of DL_Sum in summer. The predictive variables included weather variables and two disease risk indices derived based on two other empirical disease warning systems developed in Europe and North America. Relative humidity (RH) was identified the best predictive variable among all variables. Ordinal logistic regression identified mean temperature and days of heavy rainfall (>7 mm) as key weather factors for disease development. In general, RH was more important for infection process, and temperatures and rainfall were more important for symptom development and spore dispersal. Canopy structures could also have significant effects on disease development. These results may help for the development of new disease warning or forecast systems more suitable for this disease in southern China.

Amyloidogenic Nanoplaques in Blood Serum of Patients with Alzheimer's Disease Revealed by Time-Resolved Thioflavin T Fluorescence Intensity Fluctuation Analysis.

Background:Biomarkers are central to current research on molecular mechanisms underlying Alzheimer’s disease (AD). Their further development is of paramount importance for understanding pathophysiological processes that eventually lead to disease onset. Biomarkers are also crucial for early disease detection, before clinical manifestation, and for development of new disease modifying therapies.Objective:The overall aim of this work is to develop a minimally invasive method for fast, ultra-sensitive and cost-effective detection of structurally modified peptide/protein self-assemblies in the peripheral blood and in other biological fluids. Specifically, we focus here on using this method to detect structured amyloidogenic oligomeric aggregates in the blood serum of apparently healthy individuals and patients in early AD stage, and measure their concentration and size.Methods:Time-resolved detection of Thioflavin T (ThT) fluorescence intensity fluctuations in a sub-femtoliter observation volume element was used to identify in blood serum ThT-active structured amyloidogenic oligomeric aggregates, hereafter called nanoplaques, and measure with single-particle sensitivity their concentration and size.Results:The concentration and size of structured amyloidogenic nanoplaques are significantly higher in the blood serum of individuals diagnosed with AD than in control subjects.Conclusion:A new method with the ultimate, single-particle sensitivity was successfully developed. The proposed approach neither relies on the use of immune-based probes, nor on the use of radiotracers, signal-amplification or protein separation techniques, and provides a minimally invasive test for fast and cost-effective early determination of structurally modified peptides/proteins in the peripheral blood, as shown here, but also in other biological fluids.

Pattern and predictors of paradoxical response in patients with peripheral lymph node tuberculosis.

Many of the patients with lymph node tuberculosis show 'Paradoxical Response" in the form of appearance of new lymph node (LN) or increase in the size of existing LN, development of new disease in other organ and worsening of the disease while on treatment. Reason behind such response in only selective patients is not clearly understood. We evaluated the pattern and predictors for paradoxical response(s) (PR) in patients with peripheral lymph node tuberculosis (TB). Study included patients aged > 6 years with peripheral lymphadenopathy of tubercular etiology attending a tertiary care hospital from Jan 2010 to Dec 2010. PR in our study was defined as worsening of pre-existing disease or development of new lesions in a patient who has been on anti-TB therapy for at least 2 weeks. One hundred ten patients with peripheral lymph node TB were included. Their mean age was 27.5 ± 5 years and 68 (62%) were females. PR occurred in 28 (25%) patients, at a mean onset time of 6 weeks (range 2-12 weeks) after starting anti-TB medication. Four of these 28 patients experienced PR on two occasions. Of these, 22 (79%) patients presented with enlarged lymph nodes only, 8 (29%) with new nodes at same or different site and 2 (7%) with discharging sinus. PR was observed more in younger age group (p> 0.05), female gender (p> 0.05), unilateral lymphadenopathy (p> 0.05) and those with positive AFB on initial examination (p< 0.01). Paradoxical response in peripheral lymph node TB is associated with younger age, female gender, unilateral lymphadenopathy and those with positive AFB on initial examination.

The Multiple Sclerosis Registry of Szeged

Multiple sclerosis (MS) is a rare disease of the central nervous system considering the total population, the prevalence in Hungary is 83.9/100.000. The first MS registry was established in Denmark in the middle of the 1950's. This was followed by the establishment of several national, then international databases with the number of enrolled patients in the hundred-thousands. At the beginning, the primary goal of the registries were the epidemiological surveys, focusing on the number of patients, the prevalence, the incidence, the mortality and the co-morbidity. As of today, however, with the rapid advancement and development of new disease modifying therapies (DMT) with different effectiveness and adverse reactions, the therapeutic use of the registries became even more essential: the modern, up-to-date, well established registries become integral part of the DMTs' monitorization. The Multiple Sclerosis Registry of Szeged was first established as a "paper-based" database, then, in 2012, it was upgraded to an electronic, easily contactable and useable internet-based registry. As of today, it contains the socio-demographic and clinical data of more than 600 patients; we constantly add new patients as well as keep the registry up-to-date with the refreshment of old patients' data. Aside from the "classical" clinical data, it can be used for the recording and assessment of the MRI scans and the data on psychopathological and quality of life assessments, which are becoming more and more important in everyday MS management. The establishment of the internet-based registry incredibly helped both the monitorization of the effectiveness of DMTs, and the success of the new epidemiological and psychopathological surveys.

Prognostic value of galectin-3 in patients with heart failure.

Galectins are a family of soluble β-galactoside-binding lectins that have important role in inflammation, immunity, and cancer. Galectin-3 as a part of this lectin family plays a very important role in development of heart failure. According to recent papers, galectin-3 plasma level correlates with heart failure outcome, primarily with rehospitalisation and death from heart failure. This paper summarizes the most recent advances in galectin-3 research, with the accent on the role of galectin-3 in pathophysiology of myocardial remodelling and heart failure development—with preserved and reduced ejection fraction, and some implication on development of new disease modifying drugs.

Interplay of air pollution and asthma immunopathogenesis: a focused review of diesel exhaust and ozone.

Controlled human exposure experiments with diesel exhaust particles (DEPs) and ozone serve to illustrate the important role pollutants play in modulating both allergic mechanisms and immune responses to affect the immunopathogenesis of airway diseases such as asthma. For DEP, evidence is stronger for the exacerbation of existing asthma rather than for the development of new disease. To the extent that this enhancement occurs, the augmentation of Th2-type immunity seems to be a common element. For ozone, neutrophilic inflammation, altered immune cell phenotype and function and oxidative stress are all marked responses that likely contribute to underlying immune-inflammatory features of asthma. Evidence is also emerging that unique gene signatures and epigenetic control of immune and inflammatory-based genes are playing important roles in the magnitude of the impact ozone is having on respiratory health. Indeed, the interplay between air pollutants such as DEP and ozone and asthma immunopathogenesis is an ongoing concern in terms of understanding how exposure to these agents can lead to worsening of disease. To this end, asthmatics may be pre-disposed to the deleterious effects of pollutants like ozone, having constitutively modified host defense functions and gene signatures. Although this review has utilized DEP and ozone as example pollutants, more research is needed to better understand the interplay between air pollution in general and asthma immumopathogenesis.

Utility of (1–3)-β-d-Glucan Testing for Diagnostics and Monitoring Response to Treatment During the Multistate Outbreak of Fungal Meningitis and Other Infections

The 2012 outbreak of fungal meningitis associated with contaminated methylprednisolone produced by a compounding pharmacy has resulted in >750 infections. An important question facing patients and clinicians is the duration of antifungal therapy. We evaluated (1-3)-β-d-glucan (BDG) as a marker for monitoring response to treatment. We determined sensitivity and specificity of BDG testing using the Fungitell assay, by testing 41 cerebrospinal fluid (CSF) specimens from confirmed cases of fungal meningitis and 66 negative control CSF specimens. We also assessed whether BDG levels correlate with clinical status by using incident samples from 108 case patients with meningitis and 20 patients with serially collected CSF. A cutoff value of 138 pg/mL provided 100% sensitivity and 98% specificity for diagnosis of fungal meningitis in this outbreak. Patients with serially collected CSF were divided into 2 groups: those in whom BDG levels declined with treatment and those in whom BDG remained elevated. Whereas most patients with a decline in CSF BDG had clinical improvement, all 3 patients with continually elevated BDG had poor clinical outcomes (stroke, meningitis relapse, or development of new disease). Our data suggest that measuring BDG in CSF is a highly sensitive test for diagnosis of fungal meningitis in this outbreak. Analysis of BDG levels in serially collected CSF demonstrated that BDG may correlate with clinical response. Routine measurement of BDG in CSF may provide useful adjunctive data for the clinical management of patients with outbreak-associated meningitis.

Five years after the SYNTAX trial: what have we learnt?

Five years after the SYNTAX trial: what have we learnt?

Temporal analysis of intratumoral metabolic heterogeneity characterized by textural features in cervical cancer.

The aim of this pilot study was to explore heterogeneity in the temporal behavior of intratumoral [(18)F]fluorodeoxyglucose (FDG) accumulation at a regional scale in patients with cervical cancer undergoing chemoradiotherapy. Included in the study were 20 patients with FIGO stages IB1 to IVA cervical cancer treated with combined chemoradiotherapy. Patients underwent FDG PET/CT before treatment, during weeks 2 and 4 of treatment, and 12 weeks after completion of therapy. Patients were classified based on response to therapy as showing a complete metabolic response (CMR), a partial metabolic response (PMR), or residual disease and the development of new disease (NEW). Based on the presence of residual primary tumor following therapy, patients were divided into two groups, CMR and PMR/NEW. Temporal profiles of intratumoral FDG heterogeneity as characterized by textural features at a regional scale were assessed and compared with those of the standardized uptake value (SUV) indices (SUVmax and SUVmean) within the context of differentiating response groups. Textural features at a regional scale with emphasis on characterizing contiguous regions of high uptake in tumors decreased significantly with time (P < 0.001) in the CMR group, while features describing contiguous regions of low uptake along with those measuring the nonuniformity of contiguous isointense regions in tumors exhibited significant temporal changes in the PMR/NEW group (P < 0.03) but showed no persistent trends with time. Both SUV indices showed significant changes during the course of the disease in both patient groups (P < 0.001 for SUVmax and SUVmean in the CMR group; P = 0.0109 and 0.0136, respectively, for SUVmax and SUVmean in the PMR/NEW group), and also decreased at a constant rate in the CMR group and decreased up to the 4th week of treatment and then increased in the PMR/NEW group. The temporal changes in the heterogeneity of intratumoral FDG distribution characterized at a regional scale using image-based textural features may provide an adjunctive or alternative option for understanding tumor response to chemoradiotherapy and interpreting FDG accumulation dynamics in patients with malignant cervical tumors during the course of the disease.

Patterns of Recurrence Following Complete Response to Regional Chemotherapy for In-Transit Melanoma

Even after complete response (CR) to regional chemotherapy for in-transit melanoma, many patients develop recurrence. Understanding the probability, location, and timing of recurrences can optimize management strategies for this patient population. A prospective database identified patients who underwent 81 first-time hyperthermic isolated limb perfusions (HILPs) and 133 first-time isolated limb infusions (ILIs). Response was defined using the response evaluation criteria in solid tumors; recurrence was defined as development of new disease after in-field CR. HILP exhibited a significantly higher CR rate than ILI (44 vs. 28 %, p = .01). Among 36 HILP-CRs and 37 ILI-CRs, the 3-year recurrence rate was 65 % (95 % confidence interval [95 % CI]: 43-79 %) and 85 % (95 % CI: 63-94%), respectively. Median time to first recurrence was longer for HILP-CR than ILI-CR (23 vs. 8 months, p = .02). There was no statistically significant difference in median time to in-field recurrence between HILP-CR and ILI-CR (46 vs. 25 months, p = .15), but HILP-CR showed a longer median time to out-of-field recurrence (42 vs. 14 months, p = .02). Finally, the overall survival (OS) difference between HILP-CR and ILI-CR (3-year survival: 77 vs. 54 %) did not achieve statistical significance (p = .10). In the largest series comparing patterns of recurrence, we demonstrate that out-of-field recurrence after CR to HILP occurs later than after CR to ILI, though control of in-field disease remains similar. There remains no statistically significant difference in overall survival after CR to the 2 procedures.

Adjacent Level Degeneration in the Cervical Spine

Cervical arthrodesis is a common and effective procedure for treating cervical disc herniation and spondylosis causing myelopathy and/or radiculopathy. Patients undergoing cervical arthrodesis often have excellent outcomes, although approximately 25% will develop new or recurrent symptoms within 10 years after their index procedures. Whether these recurrent symptoms represent a progression of the initial disease process destined to occur with time or are a consequence of the increased stress associated with the index surgical fusion is still a matter of debate. However, risk factors have been identified that are associated with the development of new disease at adjacent levels, including (1) a single-level index surgical arthrodesis, (2) the presence of adjacent level degeneration at the time of the index surgery, and (3) fusions ending adjacent to the most common levels of cervical degeneration (C5–C6 and C6–C7). Once adjacent level disease has occurred, many patients will require a second surgical procedure either through an anterior, posterior, or combined anterior–posterior approach.

Use of laboratory and imaging investigations in dementia

The diagnosis of dementia is a complicated enterprise. This is partly caused by the insidious onset of most diseases that cause dementia. The difficulty is clearly captured in the question:...

Ocular disease in pregnancy

Pregnancy may cause ocular changes, both physiologic and pathologic, and may be associated with the development of new disease or may alter the course of preexisting disease. This paper discusses these changes and reviews diabetic retinopathy, uveitis, preeclampsia, cortical blindness and central serous chorioretinopathy. Recent reports have contributed to our understanding of the pathophysiology of diabetic retinopathy and cortical blindness associated with preeclampsia, the impact of pregnancy on the course of inflammatory eye disease, and the use of optical coherence tomography in following central serous chorioretinopathy in pregnant women. This improved understanding of the pathophysiology of ocular disease in pregnancy and the impact of pregnancy on the course of preexisting ocular disease offers the opportunity for meaningful counseling of women who are pregnant or planning to become pregnant.

Medical Issues in Treating Renal Transplant Patients

As the survival of renal transplant patients has increased, so has their risk of significant morbidity. Immunosuppressive drugs can exacerbate preexisting conditions and promote development of new disease. Effective long-term care of transplant recipients requires an understanding of how these drugs affect clinical evaluations and treatments.

Longitudinal changes in body mass index and body composition over 3 years and relationship to health outcomes in Hong Kong Chinese age 70 and older.

To determine longitudinal changes in body mass index (BMI) and body composition with age and the relationship between these changes with mortality, morbidity, functional capacity, and other health outcome measures. A 3-year longitudinal study of a random sample of community-living subjects. Older Chinese in the Hong Kong Special Administrative Region of China. Two thousand and thirty-two Chinese subjects age 70 and older recruited territory-wide by proportional random sampling. Baseline information collected included medical history, self-perceived health, Barthel Index, Geriatric Depression Score, time taken to complete a 16-foot walk, height, weight, mid-arm circumference, arm skin-fold thickness, and waist/hip ratio. Body composition was calculated from prediction equation. Outcome measures included mortality, development of new diseases, Barthel Index, time taken for 16-foot walk, self-perceived health, and Geriatric Depression Score. All parameters, with the exception of triceps skin-fold thickness in men, decreased, regardless of presence or absence of disease. The decrease in arm circumference, triceps skin-fold thickness, and total body fat (TBF) was greater in women than in men, whereas men had a greater decrease in fat-free mass (FFM). Even in the absence of disease, three times as many subjects lost > or =5kg in weight as gained > or =5kg (15% vs. 5%), and only age could be identified as a contributing factor to this weight loss. In the absence of disease, lower anthropometric indices were associated with greater mortality, development of new disease (in women only), dependency, and poor performance measure. Waist-hip ratio was not associated with mortality or any other health outcomes. Decrease in both FFM and TBF were associated with worse outcomes, the effect being more marked in women. In the older population, changes in weight and body composition occur even in the absence of disease and are associated with mortality and physical functioning level. Weight loss rather than weight gain appears to be more important in this population, and promotion of life-style interventions targeted at weight maintenance would be important.

The influence of income on morbidity, mortality and dependency in elderly Hong Kong Chinese

The association between income and mortality, morbidity and dependency is examined in a 3-year prospective follow-up study of 2032 subjects aged 70 years and above in the Hong Kong Special Administrative Region, China. Subjects were recruited using stratified disproportional random sampling of the Old Age and Disability Allowance Schemes, covering over 90% of the population. Subjects were interviewed at baseline and after 36 months. Presence or absence of disease was based on self-report of doctor diagnosis together with a check of medication taken. Functional status was measured using the Barthel Index. For the disease analysis, subjects with the disease being analyzed at baseline were excluded; similarly for the dependency analysis, subjects who were dependent at baseline were excluded. Chi-square test, univariate and multiple logistic regression were used to examine the association between income and mortality, development of new disease, and dependency. There was no association between income and mortality, or with development of new disease. Development of dependency was associated with lower income at baseline. An income of less than HK$1000 per month increased the risk of dependency by 1.8-fold (95%CI 1.1–2.9). However, this association disappeared after adjustment for age and sex. Absolute income is not an important factor contributing to mortality, morbidity and dependency in elderly Chinese aged 70 years and above. A freely accessible health and social service at low or no cost, the survivor effect, or other factors may account for the lack of association with income, contrary to findings from studies of whole populations worldwide. Therefore manipulating income alone is unlikely to affect these outcomes in the elderly.

Multiple stent implantation in single coronary arteries: acute results and six-month angiographic follow-up.

A total of 147 stents were implanted (in overlapping manner in 76% of vessels) in a single coronary artery in 59 patients (60 vessels, 97 lesions, 2.45 stents/vessel) over a period of 18 mo using high pressure stent deployment without ultrasound guidance. The indications for stenting were suboptimal percutaneous transluminal coronary angioplasty (PTCA) result (45%), primary prevention of restenosis (44%), acute closure (10%), and restenosis after plain balloon angioplasty (1%). One patient required emergency coronary artery bypass grafting (CABG) (extensive dissection), and one required early intervention with plain balloon angioplasty and intracoronary urokinase for stent thrombosis. There were no deaths. Thirteen patients had recurrence of angina within 6 mo and angiograms were performed in all. These showed intrastent restenosis in nine (all had successful repeat plain balloon angioplasty), development of new disease in other vessels along with restenosis close to the stent in the target vessel in one (underwent elective CABG) and normal angiograms with widely patent stents in three. Forty-five patients (77%) remained free of recurrent angina and 25 of these had follow-up angiograms (56%) at a mean of 172 days, two showing restenosis. Thus, the restenosis rate per patient in the symptomatic group (angiographic follow-up in 100%) was 77% and in the asymptomatic group (angiographic follow-up in 56%) was 8%. The restenosis rate in the subgroup with bailout stenting (n = 6) was 20% (angiographic follow-up in 83%). The overall restenosis rate per patient was 32% (overall angiographic follow-up in 66%). During the 6-mo follow-up period, one patient underwent elective CABG (1.7%), one sustained a non-Q myocardial infarction (1.7%), nine had repeat PTCA to the target vessel (15.5%), and there were no deaths. The event-free survival rate was 77%. Multiple stent implantation aided by high pressure stent deployment without ultrasound guidance and with adjunctive optimal antiplatelet therapy without oral anticoagulation seems to be a useful and effective revascularisation strategy to deal with long lesions and acute dissections with a high procedural success rate. The restenosis rate is acceptable and is not appreciably high as reported in previous studies from the "warfarin era."

Descriptive epidemiology of asthma

Descriptive epidemiology of asthma

Progression of renal artery fibromuscular dysplasia in 42 patients as seen on angiography.

Forty-two hypertensive patients with fibromuscular dysplasia who had angiographic evidence of the development of new disease or of the progression of existing disease were studied. Renal arterial disease was classified as medial fibroplasia with aneurysms (12 patients), subadventitial fibroplasia (24 patients), or intimal fibroplasia (6 patients). Progression of the disease was shown in all 42 patients during the follow-up period (from 1 month to 11 years and 4 months). The results indicate that all forms of fibromuscular dysplasia are progressive and have variable rates of progression.