Global matters of epidemiology and the ethical challenges of addressing the health of populations.

PURPOSE: The American College of Epidemiology (ACE) held its 2022 Annual Meeting, September 8-11, with a conference theme of 'Pandemic of Misinformation: Building Trust in Epidemiology'. The ACE Ethics Committee hosted a symposium session in recognition of the global spotlight placed on epidemiology and public health due to the COVID-19 crisis. The ACE Ethics Committee invited previous Chairs of the Ethics Committee and current President of the International Epidemiological Association to present at the symposium session. This paper aims to highlight the ethical challenges presented during the symposium session. METHODS: Three speakers with diverse backgrounds representing expertize from the fields of ethics, epidemiology, public health, clinical trials, pharmacoepidemiology, statistics, law, and public policy, covering perspectives from the U.S., Europe, and Southeast Asia were selected to present on the ethical challenges in epidemiology and public health applying a global theme. Dr. D. Weed presented on 'Causation, Epidemiology and Ethics'; Dr. C.M. Pandey presented on the 'Ethical Challenges in the Practice of Digital Epidemiology'; and Dr. J. Acquavella presented on 'Departures from Scientific Objectivity: A Cause of Eroding Trust in Epidemiology.' RESULTS: The collective goal to improve the public's health was a mutually shared theme across the three distinct areas. We highlight the common ethical guidance and principle-based approaches that have served epidemiology and public health in framing and critical analysis of novel challenges, including autonomy, beneficence, justice, scientific integrity, duties to the profession and community, and developing and maintaining public trust; however, gaps remain in how best to address health inequalities and the novel emergence and pervasiveness of misinformation and disinformation that have impacted the health of the global community. We introduce an ethical framework of translational bioethics that places considerations of the social determinants of health at the forefront. CONCLUSIONS: The COVID-19 pandemic required an expedited public health response and, at the same time, placed the profession of epidemiology and public health, its system, and structures, under the microscope like never before. This article illustrates that revisiting our foundations in research and practice and orienting contemporary challenges using an ethical lens can assist in identifying and furthering the health of populations globally.

A Systematic Study of the Prevalence and Risk Factors of CKD in Uddanam, India.

INTRODUCTION: Despite reports of a high prevalence of chronic kidney disease (CKD) from the coastal Uddanam region of Andhra Pradesh, India, there are no accurate data on the distribution of kidney function abnormalities and CKD risk factors in this region. METHODS: A total of 2419 participants were recruited through multistage cluster random sampling from 67 villages. Serum creatinine and urine protein creatinine ratio were measured using validated methodologies. All abnormal estimated glomerular filtration rate (eGFR) and urine protein creatinine ratio values were reconfirmed after 3 months. A range of sociodemographic factors were evaluated for their association with CKD using Poisson regression. RESULTS: Of 2402 eligible subjects (mean ± SD age, 45.67 ± 13.29 years; 51% female), 506 (21.07%) had CKD (mean ± SD age, 51.79 ± 13.12 years; 41.3% female). A total of 246 (10.24%) had eGFR <60 ml/min/1.73 m2, whereas 371 (15.45%) had an elevated urine protein creatinine ratio (>0.15 g/g). The poststratified estimates, adjusted for age and sex distribution of the region for CKD prevalence, are 18.7% (range, 16.4%-21.0%) overall and 21.3% (range, 18.2%-24.4% ) and 16.2% (range, 13.7%-18.8%) in men and women, respectively. Older age, male sex, tobacco use, hypertension, and family history of CKD were independently associated with CKD. Compared with those with higher eGFR, those with eGFR <60 ml/min/1.73m2 were older, were more likely to be uneducated, manual laborers/farmers, or tobacco users, and were more likely to have hypertension, a family history of CKD, a diagnosis of heart disease, and a lower body mass index. Among those with low eGFR, there was no difference between those with urine protein creatinine ratio <0.15 or >0.15, except a lower frequency of males in the former. CONCLUSION: We confirmed the high prevalence of CKD in the adult population of Uddanam. The cause was not apparent in a majority. Subjects with a low eGFR with or without elevated proteinuria were phenotypically distinct from those with proteinuria and preserved eGFR. Our data suggest the need to apply a population-based approach to screening and prevention and studies to understand the causes of CKD in this region.

Emerging Trends in Microfluidics Based Devices.

One of the major challenges for scientists and engineers today is to develop technologies for the improvement of human health in both developed and developing countries. However, the need for cost-effective, high-performance diagnostic techniques is very crucial for providing accessible, affordable, and high-quality healthcare devices. In this context, microfluidic-based devices (MFDs) offer powerful platforms for automation and integration of complex tasks onto a single chip. The distinct advantage of MFDs lies in precise control of the sample quantities and flow rate of samples and reagents that enable quantification and detection of analytes with high resolution and sensitivity. With these excellent properties, microfluidics (MFs) have been used for various applications in healthcare, along with other biological and medical areas. This review focuses on the emerging demands of MFs in different fields such as biomedical diagnostics, environmental analysis, food and agriculture research, etc., in the last three or so years. It also aims to reveal new opportunities in these areas and future prospects of commercial MFDs.

Application of student's t-test, analysis of variance, and covariance.

Student's t test (t test), analysis of variance (ANOVA), and analysis of covariance (ANCOVA) are statistical methods used in the testing of hypothesis for comparison of means between the groups. The Student's t test is used to compare the means between two groups, whereas ANOVA is used to compare the means among three or more groups. In ANOVA, first gets a common P value. A significant P value of the ANOVA test indicates for at least one pair, between which the mean difference was statistically significant. To identify that significant pair(s), we use multiple comparisons. In ANOVA, when using one categorical independent variable, it is called one-way ANOVA, whereas for two categorical independent variables, it is called two-way ANOVA. When using at least one covariate to adjust with dependent variable, ANOVA becomes ANCOVA. When the size of the sample is small, mean is very much affected by the outliers, so it is necessary to keep sufficient sample size while using these methods.

Descriptive statistics and normality tests for statistical data.

Descriptive statistics are an important part of biomedical research which is used to describe the basic features of the data in the study. They provide simple summaries about the sample and the measures. Measures of the central tendency and dispersion are used to describe the quantitative data. For the continuous data, test of the normality is an important step for deciding the measures of central tendency and statistical methods for data analysis. When our data follow normal distribution, parametric tests otherwise nonparametric methods are used to compare the groups. There are different methods used to test the normality of data, including numerical and visual methods, and each method has its own advantages and disadvantages. In the present study, we have discussed the summary measures and methods used to test the normality of the data.

Differentiation Between Crohn Disease and Intestinal Tuberculosis in Children.

OBJECTIVES: The aim of the study was to evaluate clinical, endoscopic, radiologic, and histopathological features helpful in differentiating Crohn disease (CD) from intestinal tuberculosis (ITB) in children. METHODS: Patients diagnosed to have CD or ITB based on standard recommended criteria were enrolled. Children with inflammatory bowel disease unclassified or suspected ITB or CD with incomplete work-up or lost to follow-up were excluded. The clinical and laboratory (radiology, endoscopy, and histology) details of children were analyzed. RESULTS: Twenty cases of ITB (14 [3-17] years) and 23 of CD (11 [1-17] years) were enrolled. Presentation with chronic diarrhea (82% vs 40%; P = 0.006) and blood in stool (74% vs 10%; P = 0.001) favored CD, whereas subacute intestinal obstruction (20% vs 0%; P = 0.04) and ascites (30% vs 0%; P = 0.005) favored ITB. Presence of deep ulcers (61% vs 30%; P = 0.04), longitudinal ulcers (48% vs 15%; P = 0.02), involvement of multiple colonic segments (70% vs 35%; P = 0.02), left-sided colon (87% vs 40%; P = 0.003), extraintestinal manifestations (21.7% vs 0%; P = 0.02), and higher platelet count (3.9 vs 2.6 × 10/mm; P = 0.02) favored CD. Isolated ileocecal involvement (40% vs 8.7%; P = 0.03) was a feature of ITB. TB bacilli were demonstrated in 40% ITB cases (colon-6, ascites-1, abdominal lymph node-1). On multivariate analysis, presence of blood in stool (odds ratio: 37.5 [confidence interval: 3.85-365.72], P = 0.002) and left-sided colonic involvement (odds ratio: 16.2 [confidence interval: 1.63-161.98], P = 0.02) were independent predictors of CD. CONCLUSIONS: Microbiologic confirmation of tuberculosis is possible in 40% ITB cases. Presence of blood in stool and left-sided colonic involvement are the most important features favoring CD.

Microfluidics Based Point-of-Care Diagnostics.

Point-of-care (POC) diagnostic devices have been predicted to provide a boon in health care especially in the diagnosis and detection of diseases. POC devices have been found to have many advantages like a rapid and precise response, portability, low cost, and non-requirement of specialized equipment. The major objective of a POC diagnostic research is to develop a chip-based, self-containing miniaturized device that can be used to examine different analytes in complex samples. Further, the integration of microfluidics (MF) with advanced biosensor technologies is likely to result in improved POC diagnostics. This paper presents the overview of the different materials (glass, silicon, polymer, paper) and techniques for the fabrication of MF based POC devices along with their wide range of biosensor applications. Besides this, the authors have presented in brief the challenges that MF is currently facing along with possible solutions that may result in the availability of the accessible, reliable, and cost-efficient technology. The development of these devices requires the combination of developed MF components into POC devices that are user-friendly, sensitive, stable, accurate, low cost, and minimally invasive. These MF based POC devices have tremendous potential in providing improved healthcare including easy monitoring, early detection of disease, and increased personalization.

A weighted angiographic scoring model (W-CTO score) to predict success of antegrade wire crossing in chronic total occlusion: analysis from a single centre.

Aims: The aim of this study was to derive a weighted score model predicting success/failure of antegrade wire crossing in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Methods and results: Four hundred and four consecutive CTO cases (408 lesions) undergoing CTO-PCI between January 2009 and March 2015 were included. Data were divided into two sets, namely "derivation" and "validation", in a 70:30 ratio. The score was derived using multivariate analysis to identify independent predictors of wire crossing failure from the derivation set (n=285 lesions) and validated on the remaining 123 lesions (validation set). The overall procedural success rate was 83.6%. Independent predictors of CTO-PCI failure and their contribution to the weighted score were a blunt stump (beta coefficient 2.12), length of occlusion >20 mm (beta coefficient 1.71), presence of calcification (beta coefficient 0.72), presence of tortuosity (beta coefficient 1.06) and collateral with Rentrop grade <2 (beta coefficient 1.06). The respective scores allotted were +2.0, +1.5, +1, +1, +1 (total 6.5), rounding the coefficient to the nearest 0.5. Score values of 0-2, >2-4 and >4 were classified as low, intermediate and high levels of difficulty for CTO-PCI success and were associated with 98%, 74.2%, and 42.5% (p<0.0001), respectively, of antegrade wire crossing success in the derivation set. This was also validated on the validation set with CTO success in the three derived difficulty levels being 100%, 82.4% and 48.4%, respectively. Conclusions: Our weighted angiographic CTO score is a strong predictor of final antegrade wire crossing success and could be used in day-to-day clinical practice of CTO interventions.

Diagnostic accuracy of automatic normalization of CBV in glioma grading using T1- weighted DCE-MRI.

PURPOSE: Aim of this retrospective study was to compare diagnostic accuracy of proposed automatic normalization method to quantify the relative cerebral blood volume (rCBV) with existing contra-lateral region of interest (ROI) based CBV normalization method for glioma grading using T1-weighted dynamic contrast enhanced MRI (DCE-MRI). MATERIAL AND METHODS: Sixty patients with histologically confirmed gliomas were included in this study retrospectively. CBV maps were generated using T1-weighted DCE-MRI and are normalized by contralateral ROI based method (rCBV_contra), unaffected white matter (rCBV_WM) and unaffected gray matter (rCBV_GM), the latter two of these were generated automatically. An expert radiologist with >10years of experience in DCE-MRI and a non-expert with one year experience were used independently to measure rCBVs. Cutoff values for glioma grading were decided from ROC analysis. Agreement of histology with rCBV_WM, rCBV_GM and rCBV_contra respectively was studied using Kappa statistics and intra-class correlation coefficient (ICC). RESULT: The diagnostic accuracy of glioma grading using the measured rCBV_contra by expert radiologist was found to be high (sensitivity=1.00, specificity=0.96, p<0.001) compared to the non-expert user (sensitivity=0.65, specificity=0.78, p<0.001). On the other hand, both the expert and non-expert user showed similar diagnostic accuracy for automatic rCBV_WM (sensitivity=0.89, specificity=0.87, p=0.001) and rCBV_GM (sensitivity=0.81, specificity=0.78, p=0.001) measures. Further, it was also observed that, contralateral based method by expert user showed highest agreement with histological grading of tumor (kappa=0.96, agreement 98.33%, p<0.001), however; automatic normalization method showed same percentage of agreement for both expert and non-expert user. rCBV_WM showed an agreement of 88.33% (kappa=0.76,p<0.001) with histopathological grading. CONCLUSION: It was inferred from this study that, in the absence of expert user, automated normalization of CBV using the proposed method could provide better diagnostic accuracy compared to the manual contralateral based approach.

Human Glutathione S-Transferase Enzyme Gene Polymorphisms and Their Association With Neurocysticercosis.

Neurocysticercosis (NCC), caused by cysticerci of Taenia solium is the most common helminthic infection of the central nervous system. Some individuals harboring different stages of cysticerci in the brain remain asymptomatic, while others with similar cysticerci lesions develop symptoms and the reasons remain largely unknown. Inflammatory response to antigens of dying parasite is said to be responsible for symptomatic disease. Reactive oxygen species (ROS) that are generated in inflammatory conditions can damage cellular macromolecules such as lipids, DNA, and proteins. The glutathione S-transferases (GSTs) are critical for the protection of cells from ROS. A total of 250 individuals were included in the study: symptomatic NCC = 75, asymptomatic NCC = 75, and healthy controls = 100. The individuals carrying the deletions of GSTM1 and GSTT1 were at risk for NCC (OR = 2.99, 95 %CI = 1.31-6.82, p = 0.0073 and OR = 1.94, 95 %CI = 0.98-3.82, p = 0.0550 respectively). Further, the individuals with these deletions were more likely to develop symptomatic disease (OR = 5.08, 95 % CI = 2.12-12.18, p = 0.0001 for GSTM1 and OR = 3.25, 95 %CI = 1.55-6.82, p = 0.0018 for GSTT1). Genetic variants of GSTM3 and GSTP1 were not associated with NCC. The total GST activity and levels of GSTM1, GSTT1, and GSTM3 were significantly higher in asymptomatic subjects than in symptomatic and healthy controls. Lower GST activity was observed in individuals with GSTM1 and GSTT1 deletions. The present study suggests that the individuals with GSTM1 and GSTT1 deletions are at higher risk to develop symptomatic disease. The higher GST activity and levels of GSTM1, GSTT1, and GSTM3 are likely to play role in maintaining asymptomatic condition.

Influence of immobilization and forced swim stress on the neurotoxicity of lambda-cyhalothrin in rats: Effect on brain biogenic amines and BBB permeability.

Experimental studies have been carried out on rats to understand the influence of immobilization stress (IMS), a psychological stressor and forced swim stress (FSS), a physical stressor in the neurotoxicity of lambda-cyhalothrin (LCT), a new generation type II synthetic pyrethroid with extensive applications. No significant change in plasma corticosterone levels and blood brain barrier (BBB) permeability was observed in rats subjected to IMS (one session of 15min/day), FSS (one session of 3min/day) for 28days or LCT treatment (3.0mg/kg body weight, p.o. suspended in groundnut oil) for 3days (26th, 27th and 28th day) as compared to controls. Marginal changes in the levels of biogenic amines and their metabolites (NE, EPN, DA, HVA, DOPAC, 5-HT) in hypothalamus, frontal cortex, hippocampus, and corpus striatum were observed in rats subjected to IMS or FSS or LCT alone as compared to controls. It was interesting to note that pre-exposure to IMS or FSS followed by LCT treatment for 3days caused a marked increase in plasma corticosterone levels associated with disruption in the BBB permeability as compared to rats exposed to IMS or FSS or LCT alone. Pre-exposure to IMS or FSS followed by LCT treatment for 3days resulted to alter the levels of biogenic amines and their metabolites in hypothalamus, frontal cortex, hippocampus, and corpus striatum as compared to rats exposed to IMS or FSS or LCT alone. Although neurochemical changes were more intense in rats pre-exposed to IMS as compared to those subjected to FSS on LCT treatment, the results indicate that both psychological and physical stress could be important influencing factors in the neurotoxicity of LCT.

Comparison of actual with default hematocrit value in dynamic contrast enhanced MR perfusion quantification in grading of human glioma.

PURPOSE: Dynamic contrast enhanced (DCE) MRI is used to grade and to monitor the progression of glioma while on treatment. Usually, a fixed hematocrit (Hct) value for adults is assumed to be ~45%; however, it is actually known for individual variations. Purpose of this study was to investigate the effect of measured Hct values in glioma grading using DCE-MRI. MATERIALS AND METHODS: Fifty glioma patients were included in this study. Kinetic and hemodynamic parameters were estimated for each patient using assumed as well as measured Hct values. To look the changes in Hct value over time, Hct was measured multiple times from 10 of these glioma patients who were on treatment. Simulation was done to look for the effect of extreme variations of Hct values on perfusion metrics. The data was compared to look for significant differences in the perfusion metrics derived from assumed and measured Hct values. RESULTS: The measured Hct value in patients was found to be (40.4±4.28)%. The sensitivity and specificity of DCE-MRI parameters in glioma grading were not significantly influenced by using measured vis-a-vis assumed Hct values. The serial Hct values from 10 patients who were on treatment showed a fluctuation of 15-20% over time. The simulated data showed linear influence of Hct values on kinetic parameters. The tumor grading was altered on altering the Hct values in borderline cases. CONCLUSION: Hct values influence the hemodynamic and kinetic metrics linearly and may affect glioma grading. However, perfusion metrics values might change significantly with large change in Hct values, especially in patients who are on chemotherapy necessitating its use in the DCE model.

Arterial spin labeling magnetic resonance perfusion study to evaluate the effects of age and gender on normal cerebral blood flow.

PURPOSE: Arterial spin labeling (ASL) is a noninvasive magnetic resonance (MR) perfusion technique to detect changes in blood flow. This study was undertaken to obtain a reference set of normal values of cerebral blood flow (CBF) in different age groups using three-dimensional pseudocontinuous ASL (3D PCASL) technique. The existence of an age-related decline in the gray matter (GM) and white matter (WM) CBF was evaluated. The gender-related CBF was also analyzed. MATERIALS AND METHODS: One hundred and sixty normal volunteers of varying age (6-72 years), arranged in 4 age groups, underwent MR perfusion imaging using 3D PCASL technique at 3 Tesla (T). Mean CBF values in global and regional GM and WM in different age groups were extracted from the quantitative perfusion map. RESULTS: A significant negative correlation was observed between the age and mean GM and WM CBF values (r = -0.80, P = 0.001; r = -0.59, P = 0.001, respectively). Similar results were also observed between age and various regional mean GM and WM CBF values (P = 0.001). No significant effect of gender on the GM CBF and WM CBF was found in any age group (P > 0.05). CONCLUSION: PCASL technique provides reliable quantitative parameters for the precise mapping of age-related perfusion changes occurring in the normal brain.

Influence of ApoB100 3' hypervariable repeats on acute myocardial infarction.

BACKGROUND AND OBJECTIVE: The 3' flanking region of apolipoprotein B (ApoB) 100 gene is known to contain short A+T-rich DNA sequences which are hypervariable in nature and called the variable number of tandem repeats (VNTRs). It results in different alleles of ApoB100. The present study extends the investigation of whether there is a correlation between the presence of these alleles and acute myocardial infarction (MI). METHODS: We examined ApoB genotypes in 230 acute MI patients and 300 healthy controls. PCR based genotyping was done for ApoB 3' VNTRs. RESULTS: We recoded 3'ApoB-VNTR alleles through three- and five-allelic models based on different sizes and found that large repeats (>37) were significantly associated with acute MI (p<0.0001). These large repeats (>37) were also significantly associated with higher lipid levels in the MI group. CONCLUSION: Patients with 3'ApoB-VNTR large repeats (>37) are more susceptible to acute MI development.

Comparative evaluation of 3-dimensional pseudocontinuous arterial spin labeling with dynamic contrast-enhanced perfusion magnetic resonance imaging in grading of human glioma.

INTRODUCTION: The study was performed to compare dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) with 3-dimensional (3D) pseudocontinuous arterial spin labeling (PCASL) MRI in gliomas with an aim to see whether arterial spin labeling (ASL)-derived cerebral blood flow (CBF) values can be used as an alternative to DCE-MRI for its grading. MATERIALS AND METHODS: Sixty-four patients with glioma (37 male; mean age, 43 years; 38 high grade and 26 low grade) underwent 3D-PCASL and DCE-MRI. The DCE indices (relative cerebral blood volume, rCBV; relative CBF, rCBF; permeability, k and kep; and leakage, ve) and ASL (absolute and rCBF) values were quantified from the tumors. Student independent t test was used to compare ASL and DCE-MRI indices. Pearson correlation was used to see correlation between DCE- and ASL-derived CBF values in tumor and normal parenchyma. RESULTS: On Student t test, neither ASL-derived absolute CBF (P = 0.78) nor rCBF (P = 0.12) values were found to be significantly different in 2 groups, whereas DCE indices except ve were significantly higher in high-grade gliomas. Arterial spin labeling-derived rCBF values weakly correlated with DCE-derived rCBF values, whereas these did not show correlation in normal grey (P = 0.12, r = 0.2) and white (P = 0.26, r = 0.14) matter regions. CONCLUSIONS: Three-dimensional pseudocontinuous arterial spin labeling does not appear to be a reliable technique in the current form and may not be a suitable replacement for DCE in grading of glioma.

Subcompartmentalization of extracellular extravascular space (EES) into permeability and leaky space with local arterial input function (AIF) results in improved discrimination between high- and low-grade glioma using dynamic contrast-enhanced (DCE) MRI.

PURPOSE: To modify the generalized tracer kinetic model (GTKM) by introducing an additional tissue uptake leakage compartment in extracellular extravascular space (LTKM). In addition, an implicit determination of voxel-wise local arterial input function (AIF) Cp (t) was performed to see whether these changes help in better discrimination between low- and high-grade glioma using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). MATERIALS AND METHODS: The modified model (LTKM) was explored and fitted to the concentration-time curve C(t) of each voxel, in which the local AIF Cp (t) could be estimated by a time invariant convolution approximation based on a separately measured global AIF Ca (t). A comparative study of tracer kinetic analysis was performed on 184 glioma patients using DCE-MRI data on 1.5T and 3T MRI systems. RESULTS: The LTKM analysis provided more accurate pharmacokinetic parameters as evidenced by their relative constancy with respect to the length of concentration-time curve used. In addition, LTKM with local AIF resulted in improved discrimination between low-grade and high-grade gliomas. CONCLUSION: LTKM with local AIF provides more accurate estimation of physiological parameters and improves discrimination between low-grade and high-grade gliomas as compared with GTKM.

Utility of multiparametric 3-T MRI for glioma characterization.

INTRODUCTION: Accurate grading of cerebral glioma using conventional structural imaging techniques remains challenging due to the relatively poor sensitivity and specificity of these methods. The purpose of this study was to evaluate the relative sensitivity and specificity of structural magnetic resonance imaging and MR measurements of perfusion, diffusion, and whole-brain spectroscopic parameters for glioma grading. METHODS: Fifty-six patients with radiologically suspected untreated glioma were studied with T1- and T2-weighted MR imaging, dynamic contrast-enhanced MR imaging, diffusion tensor imaging, and volumetric whole-brain MR spectroscopic imaging. Receiver-operating characteristic analysis was performed using the relative cerebral blood volume (rCBV), apparent diffusion coefficient, fractional anisotropy, and multiple spectroscopic parameters to determine optimum thresholds for tumor grading and to obtain the sensitivity, specificity, and positive and negative predictive values for identifying high-grade gliomas. Logistic regression was performed to analyze all the parameters together. RESULTS: The rCBV individually classified glioma as low and high grade with a sensitivity and specificity of 100 and 88 %, respectively, based on a threshold value of 3.34. On combining all parameters under consideration, the classification was achieved with 2 % error and sensitivity and specificity of 100 and 96 %, respectively. CONCLUSION: Individually, CBV measurement provides the greatest diagnostic performance for predicting glioma grade; however, the most accurate classification can be achieved by combining all of the imaging parameters.

Comparative assessment of therapeutic response to physiotherapy with or without botulinum toxin injection using diffusion tensor tractography and clinical scores in term diplegic cerebral palsy children.

The present study was to compare the effects of combined therapy [botulinum (BTX) plus physiotherapy] with physiotherapy alone using diffusion tensor imaging (DTI) derived fractional anisotropy (FA) values of motor and sensory fiber bundles and clinical grade of the disability to see the value of BTX in term children with spastic diplegic cerebral palsy (CP). Clinically diagnosed 36 children participated in the study. All these children were born at term, and had no history of seizures. The study was randomly categorized into two groups: group I (n=18) - physiotherapy alone and group II (n=18) - physiotherapy plus BTX injection. Quantitative diffusion tensor tractography on all these children was performed on motor and sensory fiber bundles on baseline as well as after 6months of therapy. Motor function and clinical grades were also measured by gross motor function measures (GMFM) scale on both occasions. We observed significant change in FA value in motor and sensory fiber bundle as well as in GMFM scores at 6months compared to baseline study in both the groups. However, delta change and relative delta change in FA values of sensory and motor fiber bundle as well as GMFM score between group I and group II was statistically insignificant. We conclude that addition of BTX to physiotherapy regimen does not influence the outcome at 6months with similar insult in children with term diplegic spastic CP. This information may influence management of diplegic CP especially in developing countries, where BTX is beyond the reach of these children.

Association of V249I and T280M polymorphisms in the chemokine receptor CX3CR1 gene with early onset of coronary artery disease among North Indians.

AIM: Monocytes play a critical role in atherosclerosis. CX3CR1 is expressed on monocytes and acts as either a monocyte chemokine receptor or an adhesion molecule. Two common variants of CX3CR1, V249I and T280M, reportedly decrease the coronary artery risk. RESULTS: We have examined the CX3CR1 genotype in 152 early-onset coronary artery disease (CAD) patients (age ≤ 45 years) and in 156 late-onset CAD patients (age ≥ 55 years) and in 300 healthy controls. Homozygous alleles CX3CR1-V249 and T280 were found associated with early onset of CAD (odds ratio [OR] 2.7, p<0.0001 and OR 2.76, p<0.0001, respectively), while alleles CX3CR1-I249 and M280 were found to be protective against early onset of disease (OR 0.36, p<0.0001 and OR 0.35, p<0.0001, respectively). A significant protective effect of the I(249)M(280) haplotype was observed in the early-onset CAD population (OR=0.40, 95% confidence interval [CI]=0.19-0.86, p=0.02), while the haplotype V(249)T(280) was associated with early onset of disease (OR=1.53, 95% CI=1.05-2.23, p=0.02). OBSERVATION: It might be possible that the risk of early onset of CAD is associated with a genetic variation in chemokine receptor CX3CR1.