Statistical estimation of noise induced hearing loss among the drivers in one of the most polluted cities of India.

In the present study, an attempt has been made to assess the impact of vehicular noise upon the 3-wheeler tempo drivers and to know whether there is any relationship between hearing loss and cumulative noise exposure. For this purpose, 3-wheeler tempo drivers (Exposed group) and non-commercial light motor vehicle car drivers (Unexposed group) were chosen as study subjects. Three traffic routes were selected to assess the noise level during waiting and running time in the exposed and unexposed groups. Among all three routes, the highest mean noise level (Leq) was observed on the Chowk to Dubagga route for waiting and en-route noise measurement. It was measured as 84.13 dB(A) and 86.36 dB(A) for waiting and en-route periods of 7.68 ± 3.46 and 31.05 ± 6.6 min, respectively. Cumulative noise exposure was found to be significantly different (p < 0.001) in all age groups of exposed and unexposed drivers. Audiometric tests have been performed over both exposed and unexposed groups. The regression analysis has been done keeping hearing loss among tempo drivers as the dependent variable and age (years) and Energy (Pa2 Hrs) as the independent variable using three different criteria of hearing loss definitions, i.e., World Health Organization, National Institute for Occupational Safety and Health (NIOSH), Occupational Safety and Health Administration criteria. Among these three criteria, the NIOSH criterion of hearing loss best explained the independent variables. It could explain the total variation in dependent variable by independent variable quite well, i.e., 68.1%. The finding showed a linear relationship between cumulative noise exposures (Pa2 Hrs) and the exposed group's hearing loss (dB), i.e., hearing loss increases with increasing noise dose. Based on the findings, two model equations were developed to identify the safe and unsafe noise levels with exposure time.

Exploring the association between long-term MODIS aerosol and air pollutants data across the Northern Great Plains through machine learning analysis.

Aerosol optical depth (AOD) and Ångström exponent (AE) are the major environmental indicators to perceive air quality and the impact of aerosol on climate change and health as well as the global atmospheric conditions. In the present study, an average of AOD and AE data from Tera and Aqua satellites of MODIS sensors has been investigated over 7 years i.e., from 2016 to 2022, at four locations over Northern Great Plains. Both temporal and seasonal variations over the study periods have been investigated to understand the behavior of AOD and AE. Over the years, the highest AOD and AE were observed in winter season, varying from 0.75 to 1.17 and 1.30 to 1.63, respectively. During pre-monsoon season, increasing trend of AOD varying from 0.65 to 0.95 was observed from upper (New Delhi) to lower (Kolkata) Gangetic plain, however, during monsoon and post-monsoon a reverse trend varying from 0.85 to 0.65 has been observed. Seasonal and temporal aerosol characteristics have also been analyzed and it has been assessed that biomass burning was found to be the major contributor, followed by desert dust at all the locations except in Lucknow, where the second largest contributor was dust instead of desert dust. During season-wise analysis, biomass burning was also found to be as the major contributor at all the places in all the seasons except New Delhi and Lucknow, where dust was the major contributor during pre-monsoon. A boosting regression algorithm was done using machine learning to explore the relative influence of different atmospheric parameters and pollutants with PM2.5. Water vapor was assessed to have the maximum relative influence i.e., 51.66 % followed by CO (21.81 %). This study aims to help policy makers and decision makers better understand the correlation between different atmospheric components and pollutants and the contribution of different types of aerosols.

Advances in bioelectrochemical systems for bio-products recovery.

Bioelectrochemical systems (BES) have emerged as a sustainable and highly promising technology that has garnered significant attention from researchers worldwide. These systems provide an efficient platform for the removal and recovery of valuable products from wastewater, with minimal or no net energy loss. Among the various types of BES, microbial fuel cells (MFCs) are a notable example, utilizing microbial biocatalytic activities to generate electrical energy through the degradation of organic matter. Other BES variants include microbial desalination cells (MDCs), microbial electrolysis cells (MECs), microbial electrosynthesis cells (MXCs), microbial solar cells (MSCs), and more. BESs have demonstrated remarkable potential in the recovery of diverse products such as hydrogen, methane, volatile fatty acids, precious nutrients, and metals. Recent advancements in scaling up BESs have facilitated a more realistic assessment of their net energy recovery and resource yield in real-world applications. This comprehensive review focuses on the practical applications of BESs, from laboratory-scale developments to their potential for industrial commercialization. Specifically, it highlights successful examples of value-added product recovery achieved through various BES configurations. Additionally, this review critically evaluates the limitations of BESs and provides suggestions to enhance their performance at a larger scale, enabling effective implementation in real-world scenarios. By providing a thorough analysis of the current state of BES technology, this review aims to emphasize the tremendous potential of these systems for sustainable wastewater treatment and resource recovery. It underscores the significance of bridging the gap between laboratory-scale achievements and industrial implementation, paving the way for a more sustainable and resource-efficient future.

Development, performance evaluation, and kinetic studies of microbial fuel cell based auto dripping bioelectrochemical reactor (AutoDriBER) for urine treatment.

A bioelectrochemical reactor is an assembly, which facilitates energy generation and resource recovery using electrochemically active microorganisms. To maximise energy production from wastewater in this bioreactor system special design is required. Therefore, in the present study, continuous flow auto dripping bioelectrochemical reactors (AutoDriBERs) were developed as a single and multi-electrode assembly for urine treatment. Further, their performance was assessed by connecting reactors in series and parallel arrangements. AutoDriBER configured in series connection showed the highest 93.64 ± 1.57% chemical oxygen demand removal rate with the 1.38 ± 0.64 V voltage and 2.54 W m-3 polarisation power density. The optimum flow rate for maximum voltage production was tested with various models i.e. the linear, exponential, Sweibull-1, and Sweibull-2 models to confirm voltage prediction and its validity. The Linear and exponential models were found best fitted for voltage production with R2 value of 0.999. These findings infer a novel approach toward optimisation of the complex, inexpensive and self-sufficient design for electricity generation from energy-rich urine wastewater in rural areas.

Hyperhomocysteinemia induced locked-in syndrome in a young adult due to folic acid deficiency.

'Locked-in syndrome (LIS)' is a neurological disorder, often missed initially and can have grave consequences. A rare case of LIS caused due to folic acid deficiency-induced hyperhomocysteinemia is being described here. A 16-year-old boy presented with complaints of sudden onset weakness of all the four limbs with loss of voice for one day. All the tendon reflexes were increased, bilateral planters were extensor and sensory system was intact. Patient was conscious and responded to verbal commands by ocular movements in vertical direction. Hence, a diagnosis of LIS was made. Magnetic resonance imaging of the head revealed an acute infarct in ventral pons. Serum homocysteine level was elevated (20.65 µmol/l) and folic acid level was severely low (1.7 nmol/ml). Cause of LIS was found to be hyperhomocysteinemia induced stroke in the pons, related to folic acid deficiency. The patient was managed with antiplatelet agents and folic acid supplementation and was discharged subsequently. Recognition of LIS is important as casual remarks at bedside can severely traumatize an already paralyzed but conscious and awake patient. Folic acid deficiency can lead to hyperhomocysteinemia, which can cause strokes and even LIS. Prevention of hyperhomocysteinemia may possibly prevent such neurological disasters.

Spatio-temporal assessment of ambient air quality, their health effects and improvement during COVID-19 lockdown in one of the most polluted cities of India.

The present work aims to investigate seasonal variations in air pollution levels in Lucknow and assess the ambient air quality of the city together with highlighting the health impacts of major pollutants like PM10, PM2.5, SO2, NO2, Pb, Ni and aerosols from 2010 to 2019. The maximum and minimum values of PM10, PM2.5, SO2, NO2, Pb and Ni were found to be 270.75 and 122.45 µg/m3, 124.95 and 95.52 µg/m3, 25.60 and 8.05 µg/m3, 75.65 and 23.85 µg/m3, 0.66 and 0.03 µg/m3 and 0.07 and 0.01 ng/m3, respectively. Health impact of particulate matter has also been assessed with AirQ+, and it was estimated that long-term exposure of PM10 was attributed to between 37 and 48% for post-neonatal (age 1-12 months) mortality rate due to all causes, whereas long-term attributable proportions in mortality due to exposure of PM2.5 were to about 19 to 28% from all causes. Further, an attempt has also been made to evaluate the impact of lockdown amid COVID-19 on the ambient air quality of Lucknow. During the lockdown, PM2.5 levels reduced by 65% (at Gomti Nagar), 23% (at central school), 79% (at Lalbagh) and 35% (at Talkatora), due to which, air quality index of Gomti Nagar came down to 43, well below 50 which falls in the healthy range. NO2 levels also came down. However, levels of SO2 did not show significant reduction. Correlating the data between aerosol optical depth and Angstrom exponent by Pearson correlation analysis revealed a significant positive correlation (r = 0.65, P < 0.001).

Panhypopituitarism- An unusual presenation of tuberculous meningitis.

Pituitary gland involvement is a very rare entity of central nervous system tuberculosis. Tubercular meningitis (TBM) is a chronic meningitis on hypothalamic-pituitary axis which causes high morbidity and mortality hence it is the most dreaded form of extra pulmonary tuberculosis. Here we report a case of 24 year old female presenting with three months history of fever and headache along with altered sensorium since four days. There was also complain of secondary amenorrhea and generalised apathy. Neuroimaging revealed subependymal tuberculomas with meningitis and obstructive hydrocephalus. Cerebrospinal fluid (CSF) examination was also suggestive of tubercular meningitis. Endocrinological investigations showed multiple hormonal deficiencies manifesting as pituitary hypothyroidism, hypocortisolism, hypogonadotropic hypogonadism, and hypoprolactinemia. Anti-tuberculosis treatment was started, and it led to significant improvement in the general condition of the patient.

Computational Models Accurately Predict Multi-Cell Biomarker Profiles in Inflammation and Cancer.

Individual computational models of single myeloid, lymphoid, epithelial, and cancer cells were created and combined into multi-cell computational models and used to predict the collective chemokine, cytokine, and cellular biomarker profiles often seen in inflamed or cancerous tissues. Predicted chemokine and cytokine output profiles from multi-cell computational models of gingival epithelial keratinocytes (GE KER), dendritic cells (DC), and helper T lymphocytes (HTL) exposed to lipopolysaccharide (LPS) or synthetic triacylated lipopeptide (Pam3CSK4) as well as multi-cell computational models of multiple myeloma (MM) and DC were validated using the observed chemokine and cytokine responses from the same cell type combinations grown in laboratory multi-cell cultures with accuracy. Predicted and observed chemokine and cytokine responses of GE KER + DC + HTL exposed to LPS and Pam3CSK4 matched 75% (15/20, p = 0.02069) and 80% (16/20, P = 0.005909), respectively. Multi-cell computational models became 'personalized' when cell line-specific genomic data were included into simulations, again validated with the same cell lines grown in laboratory multi-cell cultures. Here, predicted and observed chemokine and cytokine responses of MM cells lines MM.1S and U266B1 matched 75% (3/4) and MM.1S and U266B1 inhibition of DC marker expression in co-culture matched 100% (6/6). Multi-cell computational models have the potential to identify approaches altering the predicted disease-associated output profiles, particularly as high throughput screening tools for anti-inflammatory or immuno-oncology treatments of inflamed multi-cellular tissues and the tumor microenvironment.

A genomics-informed computational biology platform prospectively predicts treatment responses in AML and MDS patients.

Patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) are generally older and have more comorbidities. Therefore, identifying personalized treatment options for each patient early and accurately is essential. To address this, we developed a computational biology modeling (CBM) and digital drug simulation platform that relies on somatic gene mutations and gene CNVs found in malignant cells of individual patients. Drug treatment simulations based on unique patient-specific disease networks were used to generate treatment predictions. To evaluate the accuracy of the genomics-informed computational platform, we conducted a pilot prospective clinical study (NCT02435550) enrolling confirmed MDS and AML patients. Blinded to the empirically prescribed treatment regimen for each patient, genomic data from 50 evaluable patients were analyzed by CBM to predict patient-specific treatment responses. CBM accurately predicted treatment responses in 55 of 61 (90%) simulations, with 33 of 61 true positives, 22 of 61 true negatives, 3 of 61 false positives, and 3 of 61 false negatives, resulting in a sensitivity of 94%, a specificity of 88%, and an accuracy of 90%. Laboratory validation further confirmed the accuracy of CBM-predicted activated protein networks in 17 of 19 (89%) samples from 11 patients. Somatic mutations in the TET2, IDH1/2, ASXL1, and EZH2 genes were discovered to be highly informative of MDS response to hypomethylating agents. In sum, analyses of patient cancer genomics using the CBM platform can be used to predict precision treatment responses in MDS and AML patients.

Association of hepcidin and anemia in early chronic kidney disease.

Hepcidin is being extensively studied for anemia and inflammation in chronic kidney disease (CKD) patients. Hepcidin is thought to regulate iron metabolism by iron blockade through various mechanisms. Patients with CKD have early cardiac mortality due to anemia and subclinical inflammation; hence, we studied hepcidin as a biomarker in patients with early stage of CKD in relation to anemia and inflammation. In our cross-sectional study, a total of 80 patients were enrolled of whom, there were 25, 26, and 29 patients in CKD stages 1, 2, and 3, respectively. Patients were divided into normal iron level (39), functional iron deficiency (FID) (18), and absolute iron deficiency (AID) (23) based on transferrin saturation and ferritin. We found significantly high level of hepcidin (P <0.05) and high-sensitivity C-reactive protein (hsCRP) (P <0.05) in FID as compared to AID as well as normal iron level. We also found other inflammatory markers such as albumin, transferrin, and ferritin to be significantly associated with FID. In univariate analysis, hemoglobin (Hb) varied significantly with serum total iron-binding capacity (r = 0.40, P <0.001), log hsCRP (r = -0.32, P <0.01), and log ferritin (r = -0.23, P <0.05); however, Hb was not affected significantly with log hepcidin (r = -0.07, P >0.05). The study indicates that among early CKD patients with FID, there was high level of hepcidin along with other inflammatory parameters, which may be associated with poor cardiovascular disease outcome due to increased inflammation.

Prevalence of Myopia and Associated Risk Factors in Schoolchildren in North India.

SIGNIFICANCE: Studies reporting the prevalence and associated risk factors of myopia among schoolchildren in India are limited. Knowledge about the prevalence and the modifiable risk factors associated with myopia development will help in planning cost-effective strategies to prevent its progression in India. PURPOSE: The purpose of this study was to assess the prevalence and associated behavioral risk factors of myopia in schoolchildren in Gurugram, Haryana, in north India. METHODS: This cross-sectional study was conducted on schoolchildren (aged 5 to 15 years) from two private schools in Gurugram. Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study chart. Myopia was defined as the spherical equivalent refractive error of at least -0.50 D in the better eye. Information on the child's habits and lifestyle, study hours, hours of playing video games, and outdoor playtime were obtained using a questionnaire. Association of behavioral risk factors was analyzed for children with and without myopia, and adjusted odds ratio (OR) for each factor was estimated. RESULTS: A total of 1234 children (mean ± SD age, 10.5 ± 3 years; 59% boys) were screened. Myopia prevalence was found to be 21.1% (n = 261; mean ± SD age, 11 ± 2 years; 52% boys). The mean ± SD myopic spherical error was -1.94 ± 0.92 D. The prevalence of myopia was found to be higher (27%; 95% confidence interval, 23 to 30.6; OR, 3.19 [2.13 to 4.76]) among older children (9 to 12 years). Prevalence of myopia was more in boys (25%; 95% confidence interval, 21.1 to 28.8) compared with girls (P < .01). A positive association of presence of myopia was observed with children studying more than 4 hours per day (P < .008) and with children playing computer/video/mobile games more than 2 hours per day (P < .001). A protective effect was observed in children with outdoor activities/play for more than 1.5 hours per day (OR, 0.01 [0.00 to 0.06]). CONCLUSIONS: Myopia is a major public health concern, and its prevalence is increasing rapidly among schoolchildren in India. There is a pressing need to develop cost-effective strategies to prevent this cause of vision impairment, which can be easily treated with optical interventions.

Thyrotoxic Hypokalemic Periodic Paralysis.

Hypokalemia is a serious and life-threatening clinical condition. We present a case of a 45-year-old male, with known hyperthyroidism presenting with profound tremor, irritability, quadriparesis, and labored breathing since morning, on the day of admission. Arterial blood gas analysis showed severe hypokalemia. Patient's vital was stabilized and patient's oxygen saturation was maintained on oxygen inhalation. Intravenous potassium chloride infusion was administered with regular monitoring of vitals and electrolytes. Patient's symptoms improved. Thyroid function testing showed high free T3 (tri-iodothyronine) and free T4 (thyroxine) with low thyroid-stimulating hormone concentration in the serum, indicating thyrotoxic hypokalemic periodic paralysis. Treatment with antithyroid drug carbimazole resulted in an improvement during the follow-up visit. Hypokalemia is believed to be a consequence of a massive shift due to increased sodium-potassium-adenosine triphosphatase (Na+K+ATPase) pump activity in the presence of elevated thyroid hormones.

Agenesis of dorsal pancreas in a young adult: a rare cause of diabetes mellitus.

Dorsal pancreatic agenesis is an extremely rare entity characterised by absence of body and tail of pancreas, while there are so many other developmental anomalies of the pancreas that have been reported. Here we report a 25-year-old young man who presented with pain in the abdomen, recurrent loose stools and hyperglycaemia. On radiological imaging study, there was complete agenesis of the dorsal pancreas except for thin stripe of tissue at the level of the uncinate process. Both exocrinedysfunction and endocrine dysfunction were present in this patient. Patient was supplemented with pancreatic enzyme preparation and insulin.

The minimum test battery to screen for binocular vision anomalies: report 3 of the BAND study.

PURPOSE: This study aims to report the minimum test battery needed to screen non-strabismic binocular vision anomalies (NSBVAs) in a community set-up. When large numbers are to be screened we aim to identify the most useful test battery when there is no opportunity for a more comprehensive and time-consuming clinical examination. METHODS: The prevalence estimates and normative data for binocular vision parameters were estimated from the Binocular Vision Anomalies and Normative Data (BAND) study, following which cut-off estimates and receiver operating characteristic curves to identify the minimum test battery have been plotted. In the receiver operating characteristic phase of the study, children between nine and 17 years of age were screened in two schools in the rural arm using the minimum test battery, and the prevalence estimates with the minimum test battery were found. RESULTS: Receiver operating characteristic analyses revealed that near point of convergence with penlight and red filter (> 7.5 cm), monocular accommodative facility (< 10 cycles per minute), and the difference between near and distance phoria (> 1.25 prism dioptres) were significant factors with cut-off values for best sensitivity and specificity. This minimum test battery was applied to a cohort of 305 children. The mean (standard deviation) age of the subjects was 12.7 (two) years with 121 males and 184 females. Using the minimum battery of tests obtained through the receiver operating characteristic analyses, the prevalence of NSBVAs was found to be 26 per cent. Near point of convergence with penlight and red filter > 10 cm was found to have the highest sensitivity (80 per cent) and specificity (73 per cent) for the diagnosis of convergence insufficiency. For the diagnosis of accommodative infacility, monocular accommodative facility with a cut-off of less than seven cycles per minute was the best predictor for screening (92 per cent sensitivity and 90 per cent specificity). CONCLUSION: The minimum test battery of near point of convergence with penlight and red filter, difference between distance and near phoria, and monocular accommodative facility yield good sensitivity and specificity for diagnosis of NSBVAs in a community set-up.

Changes in stimulus and response AC/A ratio with vision therapy in Convergence Insufficiency.

PURPOSE: To evaluate the changes in the stimulus and response Accommodative Convergence to Accommodation (AC/A) ratio following vision therapy (VT) in Convergence Insufficiency (CI). METHODS: Stimulus and response AC/A ratio were measured on twenty five CI participants, pre and post 10 sessions of VT. Stimulus AC/A ratio was measured using the gradient method and response AC/A ratio was calculated using modified Thorington technique with accommodative responses measured using WAM-5500 open-field autorefractor. The gradient stimulus and response AC/A cross-link ratios were compared with thirty age matched controls. RESULTS: Mean age of the CI and control participants were 23.3±5.2 years and 22.7±4.2 years, respectively. The mean stimulus and response AC/A ratio for CI pre therapy was 2.2±0.72 and 6.3±2.0 PD/D that changed to 4.2±0.9 and 8.28±3.31 PD/D respectively post vision therapy and these changes were statistically significant (paired t-test; p<0.001). The mean stimulus and response AC/A ratio for controls was 3.1±0.81 and 8.95±2.5 PD/D respectively. CONCLUSIONS: Stimulus and response AC/A ratio increased following VT, accompanied by clinically significant changes in vergence and accommodation parameters in subjects with convergence insufficiency. This represents the plasticity of the AC/A crosslink ratios that could be achieved with vision therapy in CI.

Prevalence of non-strabismic anomalies of binocular vision in Tamil Nadu: report 2 of BAND study.

BACKGROUND: Population-based studies on the prevalence of non-strabismic anomalies of binocular vision in ethnic Indians are more than two decades old. Based on indigenous normative data, the BAND (Binocular Vision Anomalies and Normative Data) study aims to report the prevalence of non-strabismic anomalies of binocular vision among school children in rural and urban Tamil Nadu. METHODS: This population-based, cross-sectional study was designed to estimate the prevalence of non-strabismic anomalies of binocular vision in the rural and urban population of Tamil Nadu. In four schools, two each in rural and urban arms, 920 children in the age range of seven to 17 years were included in the study. Comprehensive binocular vision assessment was done for all children including evaluation of vergence and accommodative systems. In the first phase of the study, normative data of parameters of binocular vision were assessed followed by prevalence estimates of non-strabismic anomalies of binocular vision. RESULTS: The mean and standard deviation of the age of the sample were 12.7 ± 2.7 years. The prevalence of non-strabismic anomalies of binocular vision in the urban and rural arms was found to be 31.5 and 29.6 per cent, respectively. Convergence insufficiency was the most prevalent (16.5 and 17.6 per cent in the urban and rural arms, respectively) among all the types of non-strabismic anomalies of binocular vision. There was no gender predilection and no statistically significant differences were observed between the rural and urban arms in the prevalence of non-strabismic anomalies of binocular vision (Z-test, p > 0.05). The prevalence of non-strabismic anomalies of binocular vision was found to be higher in the 13 to 17 years age group (36.2 per cent) compared to seven to 12 years (25.1 per cent) (Z-test, p < 0.05). CONCLUSION: Non-strabismic binocular vision anomalies are highly prevalent among school children and the prevalence increases with age. With increasing near visual demands in the higher grades, these anomalies could significantly impact the reading efficiency of children. Thus, it is recommended that screening for anomalies of binocular vision should be integrated into the conventional vision screening protocol.

Binocular vision anomalies and normative data (BAND) in Tamil Nadu: report 1.

BACKGROUND: This population-based, cross-sectional study was designed to determine normative data for binocular vision and accommodative testing in rural and urban populations of Tamil Nadu. METHODS: A sample of 936 was determined, based on a previous pilot study. The epidemiological field work included a comprehensive eye examination and a binocular vision and accommodative assessment carried out in a total of four public schools, two each in the rural and urban arms of Chennai. An overall sample of 3,024 children between seven and 17 years of age was screened in the four schools and 920 children were included in the study. RESULTS: We found significant differences in expected values from the current clinical criteria for near point of convergence (NPC) with penlight, distance and near horizontal phorias, vergence facility, accommodation convergence/accommodation (AC/A) ratio, accommodative amplitudes, monocular and binocular accommodative facility (t-test: p < 0.001). The mean and standard deviation break/recovery values for NPC (in centimetres) with an accommodative target and penlight with red filter was 3 ± 3/4 ± 4 and 7 ± 5/10 ± 7, respectively. The mean accommodative amplitudes for the population could be estimated from the linear regression equation 16 - 0.3 × (age). The vergence facility was 12 ± 4 cycles/minute and 14 ± 4 cycles/minute in the seven to 10 and 11 to 17 age groups, respectively. Monocular accommodative facility was 11 ± 4 cycles/minute and 14 ± 5 cycles/minute and binocular accommodative facility was 10 ± 4 cycles/minute and 14 ± 5 cycles/minute in the seven to 12 and 13 to 17 age groups, respectively. The mean calculated AC/A ratio was 5.4 ± 0.6/1. CONCLUSION: The normative data for vergence and accommodative parameters for the Indian children between seven and 17 years of age are reported. The developmental trend of accommodation and vergence differences and significant differences in cut-off between the current data and available literature are reported. These differences have clinical implications for the interpretation, diagnosis and management of anomalies of binocular vision.

Computational drug treatment simulations on projections of dysregulated protein networks derived from the myelodysplastic mutanome match clinical response in patients.

Although the majority of MDS patients fail to achieve clinical improvement to approved therapies, some patients benefit from treatment. Predicting patient response prior to therapy would improve treatment effectiveness, avoid treatment-related adverse events and reduce healthcare costs. Three separate cohorts of MDS patients were used to simulate drug response to lenalidomide alone, hypomethylating agent (HMA) alone, or HMA plus lenalidomide. Utilizing a computational biology program, genomic abnormalities in each patient were used to create an intracellular pathway map that was then used to screen for drug response. In the lenalidomide treated cohort, computer modeling correctly matched clinical responses in 37/46 patients (80%). In the second cohort, 15 HMA patients were modeled and correctly matched to responses in 12 (80%). In the third cohort, computer modeling correctly matched responses in 10/10 patients (100%). This computational biology network approach identified GGH overexpression as a potential resistance factor to HMA treatment and paradoxical activation of beta-catenin (through Csnk1a1 inhibition) as a resistance factor to lenalidomide treatment. We demonstrate that a computational technology is able to map the complexity of the MDS mutanome to simulate and predict drug response. This tool can improve understanding of MDS biology and mechanisms of drug sensitivity and resistance.

Effect of epithelial cell type on in vitro invasion of non-typeable Haemophilus influenzae.

Non-typeable Haemophilus influenzae (NTHi) have been shown to have variable ability for in vitro invasion with a range of epithelial cells, and increased invasion of BEAS-2B cells has been associated with altered penicillin binding protein3 (PBP3), which is concerning as these strains are increasing worldwide. The aim of the study was to investigate the effect of respiratory cell type and the presence of altered PBP3 on the in vitro invasion of NTHi. A collection of 16 clinical NTHi isolates was established, 7 had normal PBP3, and 9 had altered PBP3 as defined by an N526K substitution. The isolates were tested for invasion of BEAS-2B, NHBE, A549 and NCI-H292 respiratory epithelial cells in vitro using a gentamicin survival assay, with invasion measured as the percentage of intracellular organisms relative to the initial inoculum. The overall median invasion for the 16 NTHi isolates for cell types BEAS-2B, NHBE, A549 and NCI-H292 cells were 3.17, 2.31, 0.11 and 1.52 respectively. The differences were statistically significant for BEAS-2B compared to A549 (P=0.015) and A549 compared to NCI-H292 (P=0.015), and there were also very marked differences in invasion for some individual isolates depending on the cell type used. There was a consistent bias for invasion of isolates with normal versus abnormal PBP3: and this was statistically significant for BEAS-2B (0.07 to 9.90, P=0.031) and A549 cells (0.02 to 1.68, P=0.037). These results show that NTHi invasion of respiratory epithelial cells in vitro is both strain dependant and influenced significantly by the cell line used, and that the association between altered PBP3 and increased invasion is conserved across multiple cell lines.