• Title/Summary/Keyword: Disease phase specificity

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Promising Pharmacological Directions in the World of Lysophosphatidic Acid Signaling

  • Stoddard, Nicole C.;Chun, Jerold
    • Biomolecules & Therapeutics
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    • v.23 no.1
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    • pp.1-11
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    • 2015
  • Lysophosphatidic acid (LPA) is a signaling lipid that binds to six known lysophosphatidic acid receptors (LPARs), named $LPA_1-LPA_6$. These receptors initiate signaling cascades relevant to development, maintenance, and healing processes throughout the body. The diversity and specificity of LPA signaling, especially in relation to cancer and autoimmune disorders, makes LPA receptor modulation an attractive target for drug development. Several LPAR-specific analogues and small molecules have been synthesized and are efficacious in attenuating pathology in disease models. To date, at least three compounds have passed phase I and phase II clinical trials for idiopathic pulmonary fibrosis and systemic sclerosis. This review focuses on the promising therapeutic directions emerging in LPA signaling toward ameliorating several diseases, including cancer, fibrosis, arthritis, hydrocephalus, and traumatic injury.

The Validity and Reliability of a Screening Questionnaire for Parkinson's Disease in a Community

  • Kim, Jong-Hun;Cheong, Hae-Kwan;Lee, Chong-Sik;Yi, Sung-Eun;Park, Kun-Woo
    • Journal of Preventive Medicine and Public Health
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    • v.43 no.1
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    • pp.9-17
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    • 2010
  • Objectives: Parkinson's disease is one of the most common neurodegenerative diseases in the elderly population. In order to estimate the prevalence of Parkinson's disease in the community, the application of a good screening tool is essential. We evaluated the validity and reliability of a Parkinson's disease screening questionnaire and propose an alternative measure to improve its validity for use in community surveys. Methods: We designed the study in a three-phase approach consisting of a screening questionnaire, neurologic examination, and confirmatory examination. A repeated survey was administered to patients with disease detected in the community and on 150 subjects. We examined internal consistency using Cronbach's alpha test, test-retest reliability using the kappa statistic, and validity using sensitivity, specificity, and ROC curves. Unadjusted odds ratios were utilized for the estimation of weights for each questionnaire item. Results: The Cronbach's alpha of the questionnaire was 0.708. The kappa statistic for test-retest reliability was good to generally fair in most of the items. When newly proposed weighting scores were used, the optimum cut-off value was 7/8. When cut-off value was 5/6 for surveying prevalence in a community, the sensitivity was 0.98, and the specificity was 0.61, with simultaneous improvement in reliability. Conclusions: We recommend 5/6 as the ideal cut-off value for the survey of PD prevalence in community. This questionnaire designed for the Korean community could help future epidemiologic studies of PD.

Endometrial histology and predictable clinical factors for endometrial disease in women with polycystic ovary syndrome

  • Park, Joon-Cheol;Lim, Su-Yeon;Jang, Tae-Kyu;Bae, Jin-Gon;Kim, Jong-In;Rhee, Jeong-Ho
    • Clinical and Experimental Reproductive Medicine
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    • v.38 no.1
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    • pp.42-46
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    • 2011
  • Objective: This study was aimed to investigate endometrial histology and to find predictable clinical factors for endometrial disease (hyperplasia or cancer) in women with polycystic ovary syndrome (PCOS). Methods: We investigated the endometrial histology and analyzed the relationship between endometrial histology and clinical parameters, such as LH, FSH, estradiol, testosterone, fasting and 2 hours postprandial glucose and insulin, insulin resistance, body mass index, endometrial thickness, menstrual status from 117 women with PCOS. Statistical analysis was performed with chi square and t-test, p-value<0.05 was considered as statistically significant. And receiver operating characteristic curve was used to find predictable clinical factors for endometrial disease and to decide the cuff off values. Results: In 117 women with PCOS, endometrial histologic profiles are as follows: proliferative phase in 90 women (76.9%), endometrial hyperplasia in 25 women (21.4%), and endometrial cancer in 2 women (1.7%). Of 25 women with endometrial hyperplasia, simple hyperplasia without atypia, complex hyperplasia without atypia and complex hyperplasia with atypia were diagnosed in 15 (12.8%), 6 (5.1%), 4 (3.4%) women, respectively. Age and endometrial thickness were significantly related with endometrial disease, p=0.013 and p=0.001, respectively. At the cut off level of 25.5 years in age, sensitivity and specificity predicting for endometrial disease were 70.4% and 55.6%, respectively (p=0.023). At the cut off level of 8.5 mm in endometrial thickness, sensitivity and specificity were 77.8% and 56.7%, respectively (p=0.000). Conclusion: In women with PCOS, the incidence of endometrial hyperplasia and cancer were 21.4% and 1.7%. The age and endometrial thickness may be used as clinical determining factors for endometrial biopsy.

Fecal Calprotectin Assay at an Early Stage of Treatment Can Be Used as a Surrogate Marker to Predict Clinical Remission and Mucosal Healing in Pediatric Crohn's Disease

  • Lee, Yeoun Joo;Park, Jae Hong
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.25 no.5
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    • pp.396-405
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    • 2022
  • Purpose: This study evaluated the predictive role of fecal calprotectin (FC) measured at an early stage of treatment for monitoring clinical remission (CR) after six months and endoscopic remission (ER) after one year of treatment in pediatric Crohn's disease (CD). Methods: This retrospective study included 45 patients who simultaneously underwent ileocolonoscopy and FC testing during follow-up. FC levels were measured before and after six weeks of treatment. CR was assessed after six months of treatment using Pediatric Crohn' s Disease Activity Index and acute-phase reactants. ER was assessed after one year using the Simple Endoscopic Score for Crohn's Disease. Results: Twenty-nine (64.4%) patients used oral prednisolone for remission induction and 16 (35.6%) patients used anti-tumor necrosis factor-alpha. Thirty (66.7%) patients achieved CR, while 24 (53.3%) achieved ER. The FC level measured after six weeks of treatment could predict CR (χ2=9.15, p=0.0025) and ER (χ2=12.31, p=0.0004). The δFC could predict CR (χ2=7.91, p=0.0049), but not ER (χ2=1.85, p=0.1738). With a threshold of ≤950.4 ㎍/g, FC at week six could predict CR with 76.7% sensitivity and 73.3% specificity. The area under the curve (AUC) was 0.769 (standard error 0.0773, p=0.0005). The same threshold predicted ER with 87.5% sensitivity and 71.4% specificity. The AUC was 0.774 (standard error 0.074, p=0.0002). Conclusion: FC assay at an early stage of treatment can be used as a surrogate marker to predict CR and mucosal healing in pediatric CD.

Establishment and application of a solid-phase blocking ELISA method for detection of antibodies against classical swine fever virus

  • Cao, Yuying;Yuan, Li;Yang, Shunli;Shang, Youjun;Yang, Bin;Jing, Zhizhong;Guo, Huichen;Yin, Shuanghui
    • Journal of Veterinary Science
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    • v.23 no.5
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    • pp.32.1-32.11
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    • 2022
  • Background: Classical swine fever (CSF) is a severe infectious disease of pigs that causes significant economic losses to the swine industry. Objectives: This study developed a solid-phase blocking enzyme-linked immunosorbent assay (spbELISA) method for the specific detection of antibodies against the CSF virus (CSFV) in porcine serum samples. Methods: A spbELISA method was developed based on the recombinant E2 expressed in Escherichia coli. The specificity of this established spbELISA method was evaluated using reference serum samples positive for antibodies against other common infectious diseases. The stability and sensitivity were evaluated using an accelerated thermostability test. Results: The spbELISA successfully detected the antibody levels in swine vaccinated with the C-strain of CSFV. In addition, the detection ability of spbELISA for CSFV antibodies was compared with that of other commercial ELISA kits and validated using an indirect immunofluorescence assay. The results suggested that the spbELISA provides an alternative, stable, and rapid serological detection method suitable for the large-scale screening of CSFV serum antibodies. Conclusions: The spbELISA has practical applications in assessing the vaccination status of large pig herds.

Comparison of Different Screening Methods in Estimating the Prevalence of Precancer and Cancer Amongst Male Inmates of a Jail in Maharashtra, India

  • Chaudhari, Amit;Hegde-Shetiya, Sahana;Shirahatti, Ravi;Agrawal, Deepti
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.859-864
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    • 2013
  • Aim: To compare the effectiveness of self-examination, clinical examination and screening methods using 1% toluidine blue and Lugol's iodine in estimating the prevalence of lesions at risk of malignancy and oral malignant disease amongst the male inmates of Yerwada Central Jail, Pune. Material and Methods: Study was carried out on male inmates in two phases. In the first phase self-examination and clinical examination was carried out on 2,257 male inmates. 164 suspicious cases were subjected to phase II of the study out of whom, 82 participants were screened with 1% toluidine blue and 2% Lugol's iodine followed by biopsy procedure. Results: Sensitivity and specificity for self-examination with clinical examination was 92.2% and 96.6% respectively. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and positive (+LR) and negative likelihood ratio (-LR) for Toluidine Blue were 88.1%, 66.6% 97.1%, 30%, 2.63 and 0.17 respectively while for Lugol's Iodine they were 94.7%, 83.8%, 98.6%, 55.5%, 5.67 and 0.06 respectively. Conclusions: Prevalence of lesions at risk of malignancy and oral malignant disease by self-examination was 7.8% and by clinical examination was 6.3%. Self-examination is an effective tool in early detection of oral cancer. Use of Lugol's iodine as a screening tool for oral lesions is highly effective in inmate populations.

Predictive factors of resistance to intravenous immunoglobulin and coronary artery lesions in Kawasaki disease

  • Lee, Hye Young;Song, Min Seob
    • Clinical and Experimental Pediatrics
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    • v.59 no.12
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    • pp.477-482
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    • 2016
  • Purpose: We conducted a study to determine which factors may be useful as predictive markers in identifying Kawasaki disease (KD) patients with a high risk of resistance to intravenous immunoglobulin (IVIG) and developing coronary artery lesions (CAL). Methods: We enrolled 287 patients in acute phase of KD at a single center. The demographic, clinical and laboratory data were collected retrospectively. Results: There were 34 patients in the IVIG resistant group. The IVIG resistant group had significantly higher serum N-terminal-pro-brain natriuretic protein (NT-proBNP) levels (P<0.01) and polymorphonuclear neutrophil (PMN) percentage (P<0.01) in comparison to the IVIG responders. The results yielded sensitivity (78.8%, 60.6%), specificity (58.2%, 90%) and cutoff value (628.6 pg/mL, 80.3%) of NT-proBNP and PMN respectively, in predicting IVIG resistance. Despite IVIG administration, 13 of the 287 patients developed CAL. The patients in the CAL group had higher NT-proBNP levels (P<0.01) and higher PMN percentage (P<0.01). In these patients, the results yielded sensitivity (73.3%, 56.7%), specificity (67.9%, 88.9%) and cutoff value (853.4 pg/mL, 80.3%) of NT-proBNP and PMN respectively, for predicting CAL. The area under the curve (AUC) for predicting resistance to IVIG was NT-proBNP 0.712, PMN 0.802. The AUC for predicting CAL was NT-proBNP 0.739, and PMN 0.773. Conclusion: Serum NT-proBNP levels and PMN percentage were significantly elevated in patients with KD with IVIG resistance and CAL. Thus, they may be useful predicting markers for IVIG resistance and development of CAL in KD patients.

Validation of a Real-Time RT-PCR Method to Quantify Newcastle Disease Virus (NDV) Titer and Comparison with Other Quantifiable Methods

  • Jang, Juno;Hong, Sung-Hwan;Kim, Ik-Hwan
    • Journal of Microbiology and Biotechnology
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    • v.21 no.1
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    • pp.100-108
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    • 2011
  • A method for the rapid detection and quantification of Newcastle disease virus (NDV) produced in an animal cell culture-based production system was developed to enhance the speed of the NDV vaccine manufacturing process. A SYBR Green I-based real-time RT-PCR was designed with a conventional, inexpensive RT-PCR kit targeting the F gene of the NDV LaSota strain. The method developed in this study was validated for specificity, accuracy, precision, linearity, limit of detection (LOD), limit of quantification (LOQ), and robustness. The validation results satisfied the predetermined acceptance criteria. The validated method was used to quantify virus samples produced in an animal cell culture-based production system. The method was able to quantify the NDV samples from mid- or late-production phases, but not effective on samples from the early-production phase. For comparison with other quantifiable methods, immunoblotting, plaque assay, and tissue culture infectious dose 50 ($TCID_{50}$) assay were also performed with the NDV samples. The results demonstrated that the real-time RT-PCR method is suitable for the rapid quantification of virus particles produced in an animal cell-culture-based production system irrespective of viral infectivity.

Survival Analysis for Prognostic Factors of Occupational Low Back Pain (직업성 요통 근로자의 장애기간에 영향을 미치는 요인 연구)

  • Kim, Ji-Yun
    • Research in Community and Public Health Nursing
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    • v.17 no.1
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    • pp.17-25
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    • 2006
  • Purpose: The goals of this research are to find out factors influencing the duration of work-related disability and to present implications for policies to prevent delayed recovery. Method: The subjects of this study were 238 workers who had been proved to be industrial disaster victims for occupational low back pain between January 1 2000 and December 31 2003. Kaplan-Meier method was used to estimate the proportion of duration of disability associated with low back pain, and Cox proportional hazards analysis was used to identify factors predicting it. The model distinguished main symptom variables affecting acute(${\leq}90\;days$) and chronic phase of disability (>90 days). Result: Fifty percent of the workers had not recovered in 408 days. The results of Cox regression show that delayed duration of disability was predicted by diagnosis, pain radiation (in chronic phase), sex, the size and labor union of the workplace, scheduled rest, compensation from the company, and operation. Conclusion: Duration of disability associated with compensated low back pain is influenced not only by factors related to the company and compensation system but also by individual factors. Thus, future efforts to reduce duration of disability may need to take into account all these factors.

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Sample size for serological surveillance of Aujeszky's disease in Korea (국내 돼지오제스키병의 혈청학적 감시활동(surveillance)을 위한 표본크기)

  • Kim, Eu-Tteum;Pak, Son-Il;Park, Choi-Kyu;Kweon, Chang-Hee
    • Korean Journal of Veterinary Research
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    • v.47 no.4
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    • pp.417-423
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    • 2007
  • Serological surveillance programs in animal populations are becoming increasingly important to estimate prevalence of a specific disease and subsequently to document disease-free status in a region or a country. For these purposes, the programs need to be based on both theoretical and economical aspects from the designing phase. From Aujeszky's disease (AD)-eradication program point of view, group of animals (aggregates, herds) not individual animal is the more important sampling unit of concern. In this study the authors therefore attempted to compute an appropriate sample size tailored to a current surveillance program against AD, assuming that the goal of this program is either herd-level prevalence estimation or documentation of AD-freedom. For prevalence estimation, assuming a finite population with imperfect sensitivity (Se) and specificity (Sp) of ELISA kit for AD diagnosis, the number of herds present, expected herd prevalence, and desired accuracy for a certain level of confidence, sample size was estimated at herd-level in the first stage and individual animal-level in the second stage. A two-stage sampling design was used to calculate a sample size to indicate AD-freedom. In this instance, the computation was based on the possible detection of a predetermined prevalence at a certain herd-level Se and Sp. This study indicated that the sample size varied with predetermined confidence, tolerance, Se and Sp at herd- and animal-level, and within- and among-herd prevalence. In general, smaller sample size was required to estimate AD prevalence than to document of AD-freedom. Compared to individual-based samples, two-stage sampling strategy requires a larger sample size to show disease-freedom. Statistical considerations including herd-level test characteristics when designing surveillance program also are further discussed.