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In order to handle second order lead processes with time delay, this paper provides a unique dominant pole placement based filtered PID controller design approach. This method does not require any finite term approximation like Pade to obtain the quasi-polynomial characteristic polynomial, arising due to the presence of the time delay term. The continuous time second order plus time delay systems with zero (SOPTDZ) are discretized using a pole-zero matching method with specified sampling time, where the transcendental exponential delay terms are converted into a finite number of poles. The pole-zero matching discretization approach with a predetermined sampling period is also used to discretize the continuous time filtered PID controller. As a result, it is not necessary to use any approximate discretization technique, such as Euler or Tustin, to derive the corresponding discrete time PID controller from its continuous time counterpart. The analytical expressions for discrete time dominant pole placement based filtered PID controllers are obtained using the coefficient matching approach, while two distinct kinds of non-dominant poles, namely all real and all complex conjugate, have been taken into consideration. The stabilizable region in the controller and design parameter space for the chosen class of linear second order time delay systems with lead is numerically approximated using the particle swarm optimization (PSO) based random search technique. The efficacy of the proposed method has been validated on a class of SOPTDZ systems including stable, integrating, unstable processes with minimum as well as non-minimum phase zeros.

Background & objectivesNo definite treatment is known for COVID-19 till date. The objective of this study is to assess the efficacy of customized Homoeopathic medicines, when used as an add-on treatment to Standard of Care (SOC), in patients suffering from moderate to severe COVID-19 infection.MethodsThis was a randomized, controlled, single-blind, parallel-group trial where 214 COVID19-positive patients were screened for moderate and severe cases of COVID-19. Adjuvant homoeopathic medicines were given in the treatment group and SOC was given to both groups. The duration of oxygen support was compared as the primary outcome. Subjects were followed for 28 days or till the end-point of mechanical ventilation/ death.ResultsOf 129 subjects included, 57 and 55 were severe; and 8 and 9 were moderate cases in Homoeopathy and SOC arms, respectively. In all, 9 (15.2%) participants in Homoeopathy and 20 (32.2%) participants in SOC arms eventually expired (pConclusionHomoeopathy, as add-on therapy with SOC for COVID-19 management, demonstrates a reduction in mortality and morbidity, by reduced requirement of oxygen and hospitalization. Some laboratory markers are normalized at an earlier time. Hence, there is overall control over the disease. Registry: The study was registered on the http://ctri.nic.in/Clinicaltrials website under identifier number: CTRI/2020/12/029668 on 9th December 2020.

The burden of type 2 diabetes (T2DM) in China is significant and growing, and this is reflected in high rates of T2DM in the city of Ningbo, China. Consequent impacts on morbidity, mortality, healthcare expenditure, and health-related quality of life, make this a problem of the utmost importance to address. One way to improve T2DM outcomes is to address lifestyle behaviours that may affect prognosis and complications, such as physical activity levels, dietary habits, smoking status, and alcohol intake. A cross-sectional survey was undertaken to describe the prevalence of being physically active, having a healthy diet, currently smoking, and currently drinking alcohol among people living with T2DM attending a diabetes clinic in Ningbo, China. Regression analysis was used to determine the factors associated with these lifestyle behaviours. We found a high prevalence of a healthy diet (97.8%, 95% CI 96.5-98.7%). Prevalence of being physically active (83.4%, 95% CI 80.6-85.9%), smoking (21.6%, 95% CI 18.8-24.6%), and alcohol drinking (32.9%. 95% CI 29.6-36.2%) appeared in keeping with those of the general population. Marked associations were demonstrated between male sex and smoking (OR 41.1, 95% CI 16.2-139.0), and male sex and alcohol drinking (OR 4.00, 95% CI 2.62-6.20). Correlation between lifestyle factors was demonstrated including between alcohol drinking and smoking, and between physical activity and reduced smoking. General diabetes self-management education programmes that address multiple lifestyle risk factors simultaneously may be beneficial in this population. Specific interventions targeting smoking cessation and reduction in alcohol drinking may be of benefit to men living with T2DM attending a diabetes clinic in Ningbo.

Human papillomavirus (HPV) induced cervical cancer is becoming a major cause of mortality in women. The present research aimed to identify the natural inhibitors of HPV-18 E1 protein (1R9W) from Himalayan herbs with lesser toxicity and higher potency. In this study, one hundred nineteen phytoconstituents of twenty important traditional medicinal plants of Northwest Himalayas were selected for molecular docking with the target protein 1R9W of HPV-18 E1 Molecular docking was performed by AutoDock vina software. ADME/T screening of the bioactive phytoconstituents was done by SwissADME, admetSAR, and Protox II. A couple of best protein-ligand complexes were selected for 100 ns MD simulation. Molecular docking results revealed that among all the selected phytoconstituents only thirty-five phytoconstituents showed the binding affinity similar or more than the standard anti-cancer drugs viz. imiquimod (-6.1 kJ/mol) and podofilox (-6.9 kJ/mol). Among all the selected thirty-five phytoconstituents, eriodictyol-7-glucuronide, stigmasterol, clicoemodin and thalirugidine showed the best interactions with a docking score of -9.1, -8.7, -8.4, and -8.4 kJ/mol. Based on the ADME screening, only two phytoconstituents namely stigmasterol and clicoemodin selected as the best inhibitor of HPV protein. MD simulation study also revealed that stigmasterol and clicoemodin were stable inside the binding pocket of 1R9W, Stigmasterol and clicoemodin can be used as a potential investigational drug to cure HPV infections.

In order to handle second order lead processes with time delay, this paper provides a unique dominant pole placement based filtered PID controller design approach. This method does not require any finite term approximation like Pade to obtain the quasi-polynomial characteristic polynomial, arising due to the presence of the time delay term. The continuous time second order plus time delay systems with zero (SOPTDZ) are discretized using a pole-zero matching method with specified sampling time, where the transcendental exponential delay terms are converted into a finite number of poles. The pole-zero matching discretization approach with a predetermined sampling period is also used to discretize the continuous time filtered PID controller. As a result, it is not necessary to use any approximate discretization technique, such as Euler or Tustin, to derive the corresponding discrete time PID controller from its continuous time counterpart. The analytical expressions for discrete time dominant pole placement based filtered PID controllers are obtained using the coefficient matching approach, while two distinct kinds of non-dominant poles, namely all real and all complex conjugate, have been taken into consideration. The stabilizable region in the controller and design parameter space for the chosen class of linear second order time delay systems with lead is numerically approximated using the particle swarm optimization (PSO) based random search technique. The efficacy of the proposed method has been validated on a class of SOPTDZ systems including stable, integrating, unstable processes with minimum as well as non-minimum phase zeros. [ABSTRACT FROM AUTHOR]

The Psyra Walker, 1860, is a typical Sino-Himalayan genus of the subfamily Ennominae, currently known by 18 species/4 subspecies globally and 9 species from India. This study aims to revise the taxonomy and ecology of Indian Psyra by providing a morphology-based diagnostic key, highlighting their altitudinal, habitat and seasonal preferences, and modelling their distribution based on current and future climatic scenarios. Here, we describe a new species, P. variabilissp. nov. and document 4 species and 1 subspecies as new to India, viz. P. gracilis, P. szetschwana, P. dsagara, P. falcipennis and P. debilis debilis, thus updating the global species count to 19 with 14 species/1 subspecies from India. We also submitted partial mitochondrial COI sequences of P. crypta, P. similaria, P. spurcataria and P. gracilis as novel to the global genetic database and calculated the overall genetic divergence was 5.17% within the genus, suggesting strong monophyly. Being a typical montane genus, most of the species of Psyra were active within 2000–2280 m altitude, 10.55–15.7°C annual mean temperature, 1200–2300 mm annual precipitation and 168–179 NDVI. Psyra species were predominant in wet temperate, mixed coniferous and moist temperate deciduous forests, their abundance and richness being at peak during post-monsoon months of October–November. The major bioclimatic variables influencing the overall distribution of the genus were mean temperature of warmest quarter, temperature seasonality and precipitation of coldest/driest quarter. While two of the modelled species were predicted to lose area occupancy under future climatic scenarios, the narrow-specialist, Trans-Himalayan species P. debilis debilis was projected to gain up to 75% additional area in the years 2041–60. The results of this study will be helpful to identify sites with maximum area loss projection in ecologically fragile Indian Himalaya and initiating conservation management for such climatically vulnerable insect species groups.

BackgroundPrecise models are necessary to estimate mortality risk following traumatic injury to inform clinical decision making or quantify hospital performance. The Trauma and Injury Severity Score (TRISS) has been the historical gold standard in survival prediction but its limitations are well-characterized. The present study used International Classification of Diseases 10th Revision (ICD-10) injury codes with machine learning approaches to develop models whose performance was compared to that of TRISS.MethodsThe 2015-2017 National Trauma Data Bank was used to identify patients following trauma-related admission. Injury codes from ICD-10 were grouped by clinical relevance into 1,495 variables. The TRISS score, which comprises the Injury Severity Score, age, mechanism (blunt vs penetrating) as well as highest 24-hour values for systolic blood pressure (SBP), respiratory rate (RR) and Glasgow Coma Scale (GCS) was calculated for each patient. A base eXtreme gradient boosting model (XGBoost), a machine learning technique, was developed using injury variables as well as age, SBP, RR, mechanism and GCS. Prediction of in-hospital survival and other in-hospital complications were compared between both models using receiver operating characteristic (ROC) and reliability plots. A complete XGBoost model, containing injury variables, vitals, demographic information and comorbidities, was additionally developed.ResultsOf 1,380,740 patients, 1,338,417 (96.9%) survived to discharge. Compared to survivors, those who died were older and had a greater prevalence of penetrating injuries (18.0% vs 9.44%). The base XGBoost model demonstrated a greater receiver-operating characteristic (ROC) than TRISS (0.950 vs 0.907) which persisted across sub-populations and secondary endpoints. Furthermore, it exhibited high calibration across all risk levels (R2 = 0.998 vs 0.816). The complete XGBoost model had an exceptional ROC of 0.960.ConclusionsWe report improved performance of machine learning models over TRISS. Our model may improve stratification of injury severity in clinical and quality improvement settings.

The identification of ancient worked materials is one of the fundamental goals of lithic use wear analysis and one of the most important parts of understanding how stone tools were used in the past. Given the documented overlaps in wear patterns generated by different materials, it is imperative to understand how individual materials’ mechanical properties might influence wear formation. Because isolating physical parameters and measuring their change is necessary for such an endeavor, controlled (rather than replicative) experiments combined with objective measurements of surface topography are necessary to better grasp how surface modifications formed on stone tools. Therefore, we used a tribometer to wear natural flint surfaces against five materials (bone, antler, beech wood, spruce wood, and ivory) under the same force, and speed, over one, three, and five hours. The study aimed to test if there is a correlation between surface modifications and the hardness of the worked material. We measured each raw material’s hardness using a nano-indentation test, and we compared the surface texture of the flint bits using a 3D optical profilometer. The interfacial detritus powder was analyzed with a scanning electron microscope to look for abraded flint particles. We demonstrate that, contrary to expectation, softer materials, such as wood, create a smoother surface than hard ones, such as ivory.

Physical parameters of the pathogenic cells, like its volume, shape, and stiffness, are important biomarkers for diseases, chemical changes within the cell, and overall cell health. The response of pathogenic bacteria and viruses to different chemical disinfectants is studied widely. Some of the routinely employed techniques to measure these changes require elaborate and expensive equipment which limits any study to a non-mobile research lab facility. Recently, we showed a micropore-based electro-fluidic technique to have great promise in measuring subtle changes in cell volumes at high throughput and resolution. This method, however, requires commercial amplifiers, which makes this technique expensive and incompatible for in-field use. In this paper, we develop a home-built amplifier to make this technique in-field compatible and apply it to measure changes in bacterial volumes upon exposure to alcohol. First, we introduce our low-cost and portable transimpedance amplifier and characterize the maximum range, absolute error percentage, and RMS noise of the amplifier in the measured current signal, along with the amplifier’s bandwidth, and compared these characteristics with the commercial amplifiers. Using our home-built amplifier, we demonstrate a high throughput detection of ~1300 cells/second and resolve cell diameter changes down to 1 μm. Finally, we demonstrate measurement of cell volume changes in E. coli bacteria when exposed to ethanol (5% v/v), which is otherwise difficult to measure via imaging techniques. Our low-cost amplifier (~100-fold lower than commercial alternatives) is battery-run, completely portable for point-of-care applications, and the electro-fluidic devices are currently being tested for in-field applications.

Foreign aid and remittances augment the income of economies. The present study examines the relationship between economic growth, poverty, inequality, remittances, and foreign aid in the Middle East and North Africa (MENA) countries using panel data methods from 1991 to 2019. The study focuses on the MENA region due to the rise in labor immigration and significant foreign aid. The empirical findings reveal that remittances, foreign aid, and economic growth play a significant role in bringing down the MENA region’s poverty levels. Besides, a rise in income share accruing to the lowest quintile is observed despite the negative income growth, which indicates that on average, the income increased more rapidly of the poor in comparison to the non-poor households. Thus, the study finds evidence supporting the hypothesis that remittances and foreign aid augment per capita income and income share in the MENA member countries.

Objectives Data on the role of helminths on diabetes in Africa are limited. We investigated whether Schistosoma and geohelminth infections are associated with β-cell function and insulin resistance among adults. Methods A cross-sectional study was conducted among adults during 2016–2017. Demography, Schistosoma and geohelminth infections, HIV and insulin data were collected. Insulin during an oral glucose tolerance test (fasting, 30, and 120-min), overall insulin secretion index, insulinogenic index, HOMA-β, and HOMA-IR were main outcome measures for β-cell function and insulin resistance, respectively. Generalized estimating equations and generalized linear models assessed the association of Schistosoma and geohelminth infections with outcome measures separately by HIV status. Outcomes were presented as marginal means with 95% CI. Results Data were obtained for 1718 participants. Schistosoma infection was associated with higher 30-min insulin (24.2 mU/L, 95% CI: 6.9, 41.6) and overall insulin secretion index (13.3 pmol/L/mmol/L; 3.7, 22.9) among HIV-uninfected participants but with lower fasting insulin (-0.9 mU/L; -1.6, -0.2), 120-min insulin (-12.0 mU/L; -18.9, -5.1), and HOMA-IR (-0.3 mmol/L; -0.6, -0.05) among HIV-infected participants not yet on antiretroviral therapy (ART). Among HIV-infected participants not on ART, geohelminth infection was associated with lower fasting insulin (-0.9 mU/L; -1.6, -0.2), 120-min insulin (-9.1 mU/L; -17.3, -1.0), HOMA-β (-8.9 mU/L)/(mmol/L; -15.3, -2.6) and overall insulin release index (-5.1 pmol/L/mmol/L; -10.3, 0.02), although this was marginally significant. There was no association among those on ART. Conclusions Schistosoma infection was associated with higher β-cell function among HIV-uninfected participants whereas Schistosoma and geohelminth infections were associated with reduced β-cell function among HIV-infected participants not on ART.

Nuclear morphological features are potent determining factors for clinical diagnostic approaches adopted by pathologists to analyze the malignant potential of cancer cells. Considering the structural alteration of the nucleus in cancer cells, various groups have developed machine learning techniques based on variation in nuclear morphometric information like nuclear shape, size, nucleus-cytoplasm ratio and various non-parametric methods like deep learning have also been tested for analyzing immunohistochemistry images of tissue samples for diagnosing various cancers. We aim to correlate the morphometric features of the nucleus along with the distribution of nuclear lamin proteins with classical machine learning to differentiate between normal and ovarian cancer tissues. It has already been elucidated that in ovarian cancer, the extent of alteration in nuclear shape and morphology can modulate genetic changes and thus can be utilized to predict the outcome of low to a high form of serous carcinoma. In this work, we have performed exhaustive imaging of ovarian cancer versus normal tissue and developed a dual pipeline architecture that combines the matrices of morphometric parameters with deep learning techniques of auto feature extraction from pre-processed images. This novel Deep Hybrid Learning model, though derived from classical machine learning algorithms and standard CNN, showed a training and validation AUC score of 0.99 whereas the test AUC score turned out to be 1.00. The improved feature engineering enabled us to differentiate between cancerous and non-cancerous samples successfully from this pilot study.

Despite rigorous sterilization protocols placed in surgical procedures, there is demonstrated evidence that show patients contract infections while hospitalized. This study aims to investigate the presence of biological materials in osteotome surgical tools after sterilization processes, determine the relationship between lack of sharpness and cross-contamination, and evaluate the influence of materials surface coating as a potential contamination preventive. Three commercially available osteotomes with different surface coatings were studied and submitted to a procedure of bone-cutting cycles. After use, each was sterilized and examined under SEM and EDS. Bone contaminants were detected in each osteotome although the PVD coated osteotome demonstrated significantly less contamination than either the as-supplied or electroless nickel coated one. According to the results, there is an association between blade sharpness and post-sterilization bone contamination. These findings suggest either disposable osteotomes should be used in surgical procedures, or an effective sharpen process should both be established and monitored to minimise post-operative infections.

Brassica juncea L. is a significant member of the Brassicaceae family, also known as Indian mustard. Water is a limiting factor in the successful production of this crop. Here, we tested the effect of water shortage in B. juncea plants supplemented with or without the application of silicon and arbuscular mycorrhizal fungi in total 8 different treatments compared under open filed conditions using a randomised complete block design (RCBD). The treatments under control conditions were control (C, T1); C+Silicon (Si, T2); C+My (Mycorrhiza; T3); and C+Si+My (T4). In contrast, treatments under stress conditions were S (Stress; T5); S+Si (T6); S+My (T7) and S+Si+My (T8), respectively. In total, we evaluated 16 traits, including plant response to stress by evaluating peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) activity. The fresh weight (g) increased only 7.47 percent with mycorrhiza (C+My) and 22.39 percent with silicon (C+Si) but increased 291.08 percent with both mycorrhiza and silicon (C+Si+My). Using mycorrhiza (S+My) or silicon (S+Si) alone produced a significant increase of 53.16 percent and 55.84 percent in fresh weight, respectively, while using both mycorrhiza and silicon (S+Si+My) together produced a dramatic increase of 380.71 percent under stress conditions. Superoxidase dismutase concentration (Ug-1 FW) was found to be increased by 29.48 percent, 6.71 percent, and 22.63 percent after applying C+My, C+Si and C+Si+My, but treatment under stress revealed some contrasting trends, with an increase of 11.21 percent and 19.77 percent for S+My, S+Si+My, but a decrease of 13.15 percent for S+Si. Finally, in the presence of stress, carotenoid content (mg/g FW) increased by 58.06 percent, 54.83 percent, 183.87 percent with C+My, and 23.81 percent with S+My and S+Si+My, but decreased by 22.22 percent with S+Si. Silicon application proved to be more effective than AMF treatment with Rhizophagus irregularis, and the best results were obtained with the combination of Si and AMF. This work will help to suggest the measures to overcome the water stress in B. juncea.

Along with the major impact on public health, the COVID-19 outbreak has caused unprecedented concerns ranging from sudden loss of employment to mental stress and anxiety. We implemented a survey-based data collection platform to characterize how the COVID-19 pandemic has affected the socio-economic, physical and mental health conditions of individuals. We focused on three broad areas, namely, changes in social interaction during home confinement, economic impact and their health status. We identified a substantial increase in virtual interaction among individuals, which might be a way to alleviate the sudden unprecedented mental health burden, exacerbated by general awareness about viral infections or other manifestations associated with them. The majority of participants (85%) lived with one or more companions and unemployment issues did not affect 91% of the total survey takers, which was one of the crucial consequences of the pandemic. Nevertheless, measures such as an increased frequency of technology-aided distant social interaction, focus on physical fitness and leisure activities were adopted as coping mechanisms during this period of home isolation. Collectively, these metrics provide a succinct and informative summary of the socio-economic and health impact of the COVID-19 pandemic on the individuals. Findings from our study reflect that continuous surveillance of the psychological consequences for outbreaks should become routine as part of preparedness efforts worldwide. Given the limitations of analyzing the large number of variables, we have made the raw data publicly available on the OMF ME/CFS Data Center server to facilitate further analyses (https://igenomed.stanford.edu/dataset/survey-study-on-lifestyle-changes-during-covid-19-pandemic).

We present further study of a subset of carbapenems, arising from a previously reported machine learning approach, with regard to their mouse pharmacokinetic profiling and subsequent study in a mouse model of sub-acute Mycobacterium tuberculosis infection. Pharmacokinetic metrics for such small molecules were compared to those for meropenem and biapenem, resulting in the selection of two carbapenems to be assessed for their ability to reduce M. tuberculosis bacterial loads in the lungs of infected mice. The original syntheses of these two carbapenems were optimized to provide multigram quantities of each compound. One of the two experimental carbapenems, JSF-2204, exhibited efficacy equivalent to that of meropenem, while both were inferior to rifampin. The lessons learned in this study point toward the need to further enhance the pharmacokinetic profiles of experimental carbapenems to positively impact in vivo efficacy performance.

BackgroundAnthrax is a major but neglected zoonotic disease of public health concern in India with Odisha contributing a major share to the disease burden. Bacillus anthracis spores can be found naturally in soil and commonly affect both animals and humans around the world. Domestic and wild animals such as cattle, sheep, goats, and deer can become infected when they inhale or ingest spores from contaminated soil, plants, or water. Anthrax can be fatal if patients are not treated promptly with antibiotics. This protocol aims to describe the implementation and evaluation of the 'One Health' intervention model based on the principles of Theory of Change (ToC) to eliminate human anthrax from a tribal district in Odisha, India.MethodsThis study would test the effectiveness of a complex public health intervention package developed using the ToC framework for the elimination of human anthrax in Koraput district by a comparative analysis of baseline and end-line data. We plan to enroll 2640 adults across 14 geographically divided blocks in Koraput district of Odisha for baseline and end-line surveys. After baseline, we would provide capacity building training to stakeholders from the department of health, veterinary, forest, academic and allied health institutions followed by workshops on sensitization and awareness through IEC (Information Education Communication)/BCC (Behavior Change Communication) activities in the community. We would establish a state-level laboratory facility as a robust system for timely diagnosis and management of human anthrax cases. Surveillance network will be strengthened to track the cases in early stage and risk zoning will be done for focused surveillance in endemic areas. Advocacy with district level administration will be done for maximizing the coverage of livestock vaccination in the entire district. Interdepartmental coordination would be established for the effective implementation of the intervention package.ConclusionThis would be a first study applying One Health concept for the elimination of human anthrax in India. The findings from this study will offer important insights for policy-making and further replication in other endemic regions of the state and country.Trial registrationThe authors confirm that all ongoing and related trials for this intervention are prospectively registered with the Clinical Trials Registry of India [CTRI/2020/05/025325] on 22 May 2020.

Abiotic stress, especially a lack of water, can significantly reduce crop yields. In this study, we evaluated the physiological and biochemical effects of potassium sulfate (K2SO4) fertilizer and varied irrigation regimes on the economically significant oilseed crop, Brassica juncea L, under open field conditions. Two cultivars (RH-725 and RH-749) of B. juncea were used in a randomized complete block design experiment with three replicates. Irrigation regimes consisted of a control (double irrigation: once at the 50% flowering and another at 50% fruiting stages), early irrigation (at 50% flowering only), late irrigation (at 50% fruiting only) and stress (no irrigation). The K2SO4 applications were: control (K0, no fertilization); K1, 10 kg ha-1; and K2, 20 kg ha-1. We measured growth via fresh and dry plant weight, plant height, root length, and leaf area. All the growth parameters were higher in RH-749. The physiological attributes, including the membrane stability index and relative water content, were higher at the 50% flowering stage in RH-749. The amount of antioxidant enzymes (catalase (CAT), guaiacol peroxidase (POX), ascorbate peroxidase (APX), and superoxide dismutase (SOD)) was enhanced when both plants were fertilized during water stress. All of these enzymes had higher activity in RH-749. The total chlorophyll content and photosynthesis rate were considerably higher in RH-749, which leaked fewer electrolytes and maintained a less destructive osmotic potential under limited water conditions. The results indicated that it is water-stress tolerant when given a high concentration of K2SO4, which alleviated the adverse effects of water stress on growth and physiology.

Optimum water availability at different growth stages is one the major prerequisites of best growth and yield production of plants. Exogenous application of plant growth regulators considered effective for normal functioning of plants under water-deficit conditions. A study was conducted to examine the influence of exogenously applied L-methionine on sunflower (Helianthus annuus L.) plants grown under water-deficit conditions. Twenty-five-day old seedlings of four sunflower cultivars, FH331, FH572, FH652 and FH623 were exposed to control (100% F.C.) and drought stress (60% F.C.) conditions. After 30-day of drought stress, L-methionine (Met; 20 mg/L) was applied as a foliar spray to control and drought stressed plants. Water deficit stress significantly reduced shoot fresh and dry weights shoot and root lengths, and chlorophyll a content in all four cultivars. While a significant increase was observed due to water deficiency in relative membrane permeability (RMP), malondialdehyde (MDA), total soluble proteins (TSP), total soluble sugars (TSS), ascorbic acid (AsA) and activity of peroxidase (POD). Although, exogenously applied Met was effective in decreasing RMP, MDA and H2O2 contents, it increased the shoot fresh weight, shoot length, chlorophyll a, chlorophyll a/b ratio, proline contents and the activities of SOD, POD and CAT enzymes in all four cultivars under water deficit stress. No change in AsA and total phenolics was observed due to foliar-applied Met under water stress conditions. Of all sunflower cultivars, cv. FH-572 was the highest and cv. FH-652 the lowest of all four cultivars in shoot fresh and dry weights as well as shoot length under drought stress conditions. Overall, foliar applied L-methionine was effective in improving the drought stress tolerance of sunflower plants that was found to be positively associated with Met induced improved growth attributes and reduced RMP, MDA and H2O2 contents under water deficit conditions.

Yield gaps of maize (Zea mays L.) in the smallholder farms of eastern India are outcomes of a complex interplay of climatic variations, soil fertility gradients, socio-economic factors, and differential management intensities. Several machine learning approaches were used in this study to investigate the relative influences of multiple biophysical, socio-economic, and crop management features in determining maize yield variability using several machine learning approaches. Soil fertility status was assessed in 180 farms and paired with the surveyed data on maize yield, socio-economic conditions, and agronomic management. The C&RT relative variable importance plot identified farm size, total labor, soil factors, seed rate, fertilizer, and organic manure as influential factors. Among the three approaches compared for classifying maize yield, the artificial neural network (ANN) yielded the least (25%) misclassification on validation samples. The random forest partial dependence plots revealed a positive association between farm size and maize productivity. Nonlinear support vector machine boundary analysis for the eight top important variables revealed complex interactions underpinning maize yield response. Notably, farm size and total labor synergistically increased maize yield. Future research integrating these algorithms with empirical crop growth models and crop simulation models for ex-ante yield estimations could result in further improvement.

INTRODUCTION:Atorvastatin-80mg/day and Rosuvastatin-40mg/day are the commonest high-dose statin (3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors) regimes for post-PCI (Percutaneous Coronary Interventions) patients to lower (by ≥50%) blood low-density-lipoprotein cholesterol (LDL-C). Dearth of conclusive evidence from developing world, regarding overall safety, tolerability and comparative effectiveness (outcome/safety/tolerability/endothelial inflammation control) of Rosuvastatin over Atorvastatin in high-dose, given its higher cost, called for an overall and comparative assessment among post-PCI patients in a tertiary cardiac-care hospital of Kolkata, India. METHODS:A record-based non-concurrent cohort study was conducted involving 942 post-PCI patients, aged 18-75 years, on high-dose statin for three months and followed up for ≥one year. Those on Atorvastatin-80mg (n = 321) and Rosuvastatin-40mg (n = 621) were compared regarding outcome (death/non-fatal myocardial infarction: MI/repeated hospitalization/target-vessel revascularisation/control of LDL and high-sensitivity C-reactive protein: hsCRP), safety (transaminitis/myopathy/myalgia/myositis/rhabdomyolysis), tolerability (gastroesophageal reflux disease: GERD/gastritis) and inflammation control adjusting for socio-demographics, tobacco-use, medications and comorbidities using SAS-9.4. RESULTS:Groups varied minimally regarding distribution of age/gender/tobacco-use/medication/comorbidity/baseline (pre-PCI) LDL and hs-CRP level. During one-year post-PCI follow up, none died. One acute MI and two target vessel revascularizations occurred per group. Repeated hospitalization for angina/stroke was 2.18% in Atorvastatin group vs. 2.90% in Rosuvastatin group. At three-months follow up, GERD/Gastritis (2.18% vs 4.83%), uncontrolled hs-CRP (22.74% vs 31.08%) and overall non-tolerability (4.67% vs. 8.21%) were lower for Atorvastatin group. Multiple logistic regression did show that compared to Atorvastatin-80mg, Rosuvastatin-40mg regime had poorer control of hs-CRP (A3OR = 1.45,p = 0.0202), higher (A3OR = 2.07) adverse effects, poorer safety profile (A3OR = 1.23), higher GERD/Gastritis (A3OR = 1.50) and poorer overall tolerability (A3OR = 1.50). CONCLUSION:Post-PCI high dose statins were effective, safe and well-tolerated. High dose Rosuvastatin as compared to high dose Atorvastatin were similar in their clinical efficacy. Patients treated with Atrovastatin had significantly lower number of patients with hs-CRP (high-sensitivity C-reactive protein)/C-reactive protein (CRP) level beyond comparable safe limit and relatively better tolerated as opposed to Rosuvastatin-40mg.Thus given the lower price, Atorvastatin 80mg/day appeared to be more cost-effective. A head-to-head cost-effectiveness as well as efficacy trial may be the need of the hour.

BACKGROUND:The purpose of this study was to assess the impact of vendor-provided atlas-based MRAC on FDG PET/MR for the evaluation of Alzheimer's disease (AD) by using simulated images. METHODS:We recruited 47 patients, from two institutions, who underwent PET/CT and PET/MR (GE SIGNA) examination for oncological staging. From the PET raw data acquired on PET/MR, two FDG-PET series were generated, using vendor-provided MRAC (atlas-based) and CTAC. The following simulation steps were performed in MNI space: After spatial normalization and smoothing of the PET datasets, we calculated the error map for each patient, PETMRAC/PETCTAC. We multiplied each of these 47 error maps with each of the 203 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases after the identical normalization and smoothing. This resulted in 203*47 = 9541 datasets. To evaluate the probability of AD in each resulting image, a cumulative t-value was calculated automatically using commercially-available software (PMOD PALZ) which has been used in multiple large cohort studies. The diagnostic accuracy for the discrimination of AD and predicting progression from mild cognitive impairment (MCI) to AD were evaluated in simulated images compared with ADNI original images. RESULTS:The accuracy and specificity for the discrimination of AD-patients from normal controls were not substantially impaired, but sensitivity was slightly impaired in 5 out of 47 datasets (original vs. error; 83.2% [CI 75.0%-89.0%], 83.3% [CI 74.2%-89.8%] and 83.1% [CI 75.6%-88.3%] vs. 82.7% [range 80.4-85.0%], 78.5% [range 72.9-83.3%,] and 86.1% [range 81.4-89.8%]). The accuracy, sensitivity and specificity for predicting progression from MCI to AD during 2-year follow-up was not impaired (original vs. error; 62.5% [CI 53.3%-69.3%], 78.8% [CI 65.4%-88.6%] and 54.0% [CI 47.0%-69.1%] vs. 64.8% [range 61.5-66.7%], 75.7% [range 66.7-81.8%,] and 59.0% [range 50.8-63.5%]). The worst 3 error maps show a tendency towards underestimation of PET scores. CONCLUSION:FDG-PET/MR based on atlas-based MR attenuation correction showed similar diagnostic accuracy to the CT-based method for the diagnosis of AD and the prediction of progression of MCI to AD using commercially-available software, although with a minor reduction in sensitivity.

To determine the prevalence of vascular complications among inpatients with type 2 diabetes mellitus (T2DM) and factors independently associated with vascular complications in a tertiary care department in Ningbo, China, the authors conducted a cross-sectional study using an existing computerised medical records database. A total of 3370 adult patients with T2DM were admitted to this tertiary care department for the first time between 2012 and 2017. Patients were categorised as those (1) with at least one vascular complication, (2) with at least one microvascular complication, and (3) with at least one macrovascular complication. Over 5 years, the prevalence of vascular, microvascular, and macrovascular complications among inpatients with T2DM was 73.2%, 57.5%, and 51.4%, respectively. The odds of vascular, microvascular, and macrovascular complications increased with age and were higher in patients with hypertension. The odds of vascular and microvascular complications were higher in single, divorced, or widowed patients, patients with T2DM for a long time, and patients on advanced T2DM therapeutic regimen. The odds of vascular and macrovascular complications were lower in women. The odds of microvascular complications decreased with education. The odds of macrovascular complications were higher in smokers. In conclusion, in the tertiary care department, more than half of inpatients with T2DM had vascular complications, and factors independently associated with vascular complications were identified. The study findings could be used in future interventional studies to prevent and manage vascular complications among these patients.

Common scab disease in potato has become a widespread issue in major potato production areas, leading to increasing economic losses. Varietal resistance is seen as a viable and long-term scab management strategy. However, the genes and mechanisms of varietal resistance are unknown. In the current study, a comparative RNA transcriptome sequencing and differential gene signaling and priming sensitization studies were conducted in two potato cultivars that differ by their response to common scab (Streptomyces scabies), for unraveling the genes and pathways potentially involved in resistance within this pathosystem. We report on a consistent and contrasted gene expression pattern from 1,064 annotated genes differentiating a resistant (Hindenburg) and a susceptible (Green Mountain) cultivars, and identified a set of 273 co-regulated differentially expressed genes in 34 pathways that more likely reflect the genetic differences of the cultivars and metabolic mechanisms involved in the scab pathogenesis and resistance. The data suggest that comparative transcriptomic phenotyping can be used to predict scab lesion phenotype in breeding lines using mature potato tuber. The study also showed that the resistant cultivar, Hindenburg, has developed and maintained a capacity to sense and prime itself for persistent response to scab disease over time, and suggests an immune priming reaction as a mechanism for induced-resistance in scab resistant potato cultivars. The set of genes identified, described, and discussed in the study paves the foundation for detailed characterizations towards tailoring and designing procedures for targeted gene knockout through gene editing and phenotypic evaluation.

To understand the cost burden of medical care it is essential to partition medical spending into conditions. Two broad strategies have been used to measure disease-specific spending. The first attributes each medical claim to the condition that physicians list as its cause. The second decomposes total spending for a person over a year to their cumulative set of health conditions. Traditionally, this has been done through regression analysis. This paper has two contributions. First, we develop a new cost attribution method to attribute spending to conditions using a more flexible attribution approach, based on propensity score analysis. Second, we compare the propensity score approach to the claims-based approach and the regression approach in a common set of beneficiaries age 65 and older in the 2009 Medicare Current Beneficiary Survey. Our estimates show that the three methods have important differences in spending allocation and that the propensity score model likely offers the best theoretical and empirical combination.

BackgroundThe burden of diabetes is increasing in sub-Saharan Africa, including among people living with HIV. We assessed the prevalence of diabetes and the roles of HIV, antiretroviral therapy (ART) and traditional risk factors among adults in Tanzania.MethodsWe analysed diabetes-relevant baseline data from 1,947 adult participants in the CICADA study in Mwanza, Tanzania: 655 HIV-uninfected, 956 HIV-infected ART-naïve, and 336 HIV-infected persons on ART. WHO guidelines for haemoglobin A1c (HbA1c) and oral glucose tolerance test (OGTT) were used to define diabetes and prediabetes. Risk factors were evaluated using multinomial logistic regression analysis. Relative risk ratios (RRR) were generated comparing participants with diabetes and prediabetes against the reference of those with no diabetes.ResultsMean age was 41 (SD 12) years; 59% were women. The prevalence of diabetes was 13% by HbA1c and 6% by OGTT, with partial overlap among participants identified by the two tests. Relative to HIV-uninfected, HIV-infected ART-naïve persons had increased relative risks of diabetes (HbA1c: RRR = 1.95, 95% CI 1.25-3.03; OGTT: RRR = 1.90, 95% CI 0.96-3.73) and prediabetes (HbA1c: RRR = 2.89, 95% CI 1.93-4.34; OGTT: RRR = 1.61, 95% CI 1.22-2.13). HIV-infected participants on ART showed increased risk of prediabetes (RRR 1.80, 95% CI 1.09, 2.94) by HbA1c, but not diabetes. CD4 count < 200 cell/μL at recruitment increased risk and physical activity decreased risk of diabetes by both HbA1c and OGTT.ConclusionsThe prevalence of diabetes was high, especially among HIV-infected ART-naïve adults. Being more physically active was associated with lower risk of diabetes. HbA1c and OGTT identified different participants as having diabetes or prediabetes. Overall, the finding of high burden of diabetes among HIV-infected persons suggests that health systems should consider integrating diabetes screening and treatment in HIV clinics to optimize the care of HIV patients and improve their health outcomes.

(-)-Oleocanthal (oleocanthal) is a phenolic compound found in varying concentrations in extra virgin olive oil oleocanthal has been shown to be active physiologically, benefiting several diseased states by conferring anti-inflammatory and neuroprotective benefits. Recently, we and other groups have demonstrated its specific and selective toxicity toward cancer cells; however, the mechanism leading to cancer cell death is still disputed. The current study demonstrates that oleocanthal, as well as naturally oleocanthal-rich extra virgin olive oils, induced damage to cancer cells' lysosomes leading to cellular toxicity in vitro and in vivo. Lysosomal membrane permeabilization following oleocanthal treatment in various cell lines was assayed via three complementary methods. Additionally, we found oleocanthal treatment reduced tumor burden and extended lifespan of mice engineered to develop pancreatic neuroendocrine tumors. Finally, following-up on numerous correlative studies demonstrating consumption of olive oil reduces cancer incidence and morbidity, we observed that extra virgin olive oils naturally rich in oleocanthal sharply reduced cancer cell viability and induced lysosomal membrane permeabilization while oleocanthal-poor oils did not. Our results are especially encouraging since tumor cells often have larger and more numerous lysosomes, making them especially vulnerable to lysosomotropic agents such as oleocanthal.

In the present two-year study, an attempt was made to estimate the grain yield, grain nutrient uptake, and oil quality of three commonly grown maize (Zea mays L.) hybrids fertilized with varied levels of nitrogen (N), phosphorus (P) and potassium (K). Results obtained from both the experimental years indicated that application of 125% of recommended dose of fertilizer (RDF) recorded maximum grain yield (10.37 t ha-1; 124% higher than control). When compared with 100% RDF, grain yield reduction with nutrient omission was 44% for N omission, 17% for P omission, and 27% for K omission. Nitrogen uptake was increased with increasing NPK levels up to 150% RDF that was statistically at par (p ≥ 0.01) with 125% RDF. Increasing trend in P and K uptake was observed with successive increase in NPK levels up to 125% RDF, above which it declined. The protein content was significantly higher in grains of var. P 3396 with 125% RDF. Nutrient management has significant (p ≤ 0.01) role in the grain oil content. Saturated fatty acids (palmitic, stearic and arachidic acid) content decreased, and unsaturated fatty acid (oleic, linoleic and linolenic acid) increased with increasing NPK levels. The average oleic acid desaturation and linoleic acid desaturation ratios were increased with increasing NPK levels up to 100 and 125% RDF, respectively. However, average monounsaturated fatty acids (MUFA): poly-unsaturated fatty acids (PUFA), saturated: unsaturated as well as linoleic: linolenic acid ratios were increased on receiving 75% RDF, and beyond that it showed decreasing trend. The omission of K had the highest inhibitory effect on corn oil quality followed by N and P omission.

Diagnostic and Statistical Manual of mental disorder-IV (DSM-IV) TR based INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD) is an established instrument for the diagnosis of ASD in Indian subcontinent and low-middle income countries (LMIC). The introduction of DSM-5 necessitated revision of existing INDT-ASD tool to incorporate the DSM-5 related changes. This study was undertaken to develop and validate the DSM-5 based All India Institute of Medical Sciences (AIIMS)-Modified-INDT-ASD Tool. The modifications were done using Delphi method and included: (a) rearrangement of questions from the previous tool; and (b) addition of new questions on sensory symptoms. The modified tool was validated against DSM-5 diagnostic criteria. In addition, receiver operating characteristic (ROC) curves were used to determine the cut-off for total score as compared to Childhood Autism Rating Scale (CARS) score to grade the severity of ASD. Two-hundred-twenty-five children (159 boys, median age = 47months) were enrolled. The modified tool demonstrated sensitivity of 98.4% and specificity of 91.7% to diagnose ASD. A score ≥14 on the tool was suggestive of severe ASD (CARS>36.5) with a sensitivity and specificity of 80% and 80.7% respectively [Area under the curve = 0.89]. AIIMS-Modified-INDT-ASD Tool is a simple and structured instrument based on DSM-5 criteria which can facilitate diagnosis of ASD with acceptable diagnostic accuracy.

The molecular chaperone Hsp90 is an essential and highly abundant central node in the interactome of eukaryotic cells. Many of its large number of client proteins are relevant to cancer. A hallmark of Hsp90-dependent proteins is that their accumulation is compromised by Hsp90 inhibitors. Combined with the anecdotal observation that cancer cells may be more sensitive to Hsp90 inhibitors, this has led to clinical trials aiming to develop Hsp90 inhibitors as anti-cancer agents. However, the sensitivity to Hsp90 inhibitors has not been studied in rigorously matched normal versus cancer cells, and despite the discovery of important regulators of Hsp90 activity and inhibitor sensitivity, it has remained unclear, why cancer cells might be more sensitive. To revisit this issue more systematically, we have generated an isogenic pair of normal and oncogenically transformed NIH-3T3 cell lines. Our proteomic analysis of the impact of three chemically different Hsp90 inhibitors shows that these affect a substantial portion of the oncogenic program and that indeed, transformed cells are hypersensitive. Targeting the oncogenic signaling pathway reverses the hypersensitivity, and so do inhibitors of DNA replication, cell growth, translation and energy metabolism. Conversely, stimulating normal cells with growth factors or challenging their proteostasis by overexpressing an aggregation-prone sensitizes them to Hsp90 inhibitors. Thus, the differential sensitivity to Hsp90 inhibitors may not stem from any particular intrinsic difference between normal and cancer cells, but rather from a shift in the balance between cellular quiescence and activity.

Metformin, a widely prescribed anti-diabetic drug, shows anticancer activity in various cancer types. Few studies documented that there was a decreased level of LDL and total cholesterol in blood serum of metformin users. Based on these views, this study aimed to determine if metformin exhibits anticancer activity by alleviating cholesterol level in cancer cells. The present study found that treatment of breast cancer MDA-MB-231 cells with metformin significantly decreased cholesterol content with concomitant inhibition of various cholesterol regulatory genes (e.g., HMGCoR, LDLR and SREBP1). Metformin decreased cell viability, migration and stemness in metastatic MDA-MB-231 cells. Similarly, metformin treatment suppressed expressions of anti-apoptotic genes BCL2 and Bcl-xL, and mesenchymal genes vimentin, N-cadherin, Zeb1 and Zeb2 with simultaneous enhancement of apoptotic caspase 3 and Bax, and epithelial genes E-cadherin and keratin 19 expressions, confirming an inhibitory effect of metformin in tumorigenesis. Similar to metformin, depletion of cholesterol by methyl beta cyclodextrin (MBCD) diminished cell viability, migration, EMT and stemness in breast cancer cells. Moreover, metformin-inhibited cell viability, migration, colony and sphere formations were reversed back by cholesterol treatment. Similarly, cholesterol treatment inverted metformin-reduced several gene expressions (e.g., Bcl-xL, BCL2, Zeb1, vimentin, and BMI-1). Additionally, zymography data demonstrated that cholesterol upregulated metformin-suppressed MMP activity. These findings suggested that metformin revealed anticancer activity by lowering of cholesterol content in breast cancer cells. Thus, this study, for the first time, unravelled this additional mechanism of metformin-mediated anticancer activity.

Phage therapy offers a potential alternate strategy for the treatment of peri-prosthetic joint infection (PJI), particularly where limited effective antibiotics are available. We undertook preclinical trials to investigate the therapeutic efficacy of a phage cocktail, alone and in combination with vancomycin, to reduce bacterial numbers within the infected joint using a clinically-relevant model of Staphylococcus aureus-induced PJI. Infected animals were randomised to 4 treatment groups, with treatment commencing 21-days post-surgery: bacteriophage alone, vancomycin alone, bacteriophage and vancomycin, and sham. At day 28 post-surgery, animals were euthanised for microbiological and immunological assessment of implanted joints. Treatment with phage alone or vancomycin alone, led to 5-fold and 6.2-fold reductions, respectively in bacterial load within peri-implant tissue compared to sham-treated animals. Compared to sham-treated animals, a 22.5-fold reduction in S. aureus burden was observed within joint tissue of animals that were administered phage in combination with vancomycin, corresponding with decreased swelling in the implanted knee. Microbiological data were supported by evidence of decreased inflammation within the joints of animals administered phage in combination with vancomycin, compared to sham-treated animals. Our findings provide further support for phage therapy as a tolerable and effective adjunct treatment for PJI.

One of the main technical challenges of PET/MRI is to achieve an accurate PET attenuation correction (AC) estimation. In current systems, AC is accomplished by generating an MRI-based surrogate computed tomography (CT) from which AC-maps are derived. Nevertheless, all techniques currently implemented in clinical routine suffer from bias. We present here a convolutional neural network (CNN) that generated AC-maps from Zero Echo Time (ZTE) MR images. Seventy patients referred to our institution for 18FDG-PET/MR exam (SIGNA PET/MR, GE Healthcare) as part of the investigation of suspected dementia, were included. 23 patients were added to the training set of the manufacturer and 47 were used for validation. Brain computed tomography (CT) scan, two-point LAVA-flex MRI (for atlas-based AC) and ZTE-MRI were available in all patients. Three AC methods were evaluated and compared to CT-based AC (CTAC): one based on a single head-atlas, one based on ZTE-segmentation and one CNN with a 3D U-net architecture to generate AC maps from ZTE MR images. Impact on brain metabolism was evaluated combining voxel and regions-of-interest based analyses with CTAC set as reference. The U-net AC method yielded the lowest bias, the lowest inter-individual and inter-regional variability compared to PET images reconstructed with ZTE and Atlas methods. The impact on brain metabolism was negligible with average errors of -0.2% in most cortical regions. These results suggest that the U-net AC is more reliable for correcting photon attenuation in brain FDG-PET/MR than atlas-AC and ZTE-AC methods.

ObjectivesTo determine the prevalence of polypharmacy prescription among type 2 diabetes (T2DM) patients at a tertiary care department in Ningbo, China, and to determine factors that independently predict this polypharmacy prescription.MethodsA retrospective cross-sectional study was conducted using an existing computerised medical records database. This database was screened from 2012 to 2017 for adult patients with T2DM and parameters like prescribed medicines and socio-demographic, behavioural and other medical information. Polypharmacy prescription was defined as the simultaneous prescription of ≥5 medicines by the clinician at the time of discharge for daily usage by the patient as part of his/her long-term treatment plan.ResultsThe study inclusion criteria were satisfied by 3370 T2DM patients. Over a 5-year period, 72.2% (n = 2432) of T2DM patients were prescribed polypharmacy. On an average, eight medicines were prescribed to them. The odds of polypharmacy prescription increased with patients' age (18-39 years: 1; 40-59 years: OR 1.86, 95% CI 1.28-2.71; and ≥60 years: 2.42, 1.65-3.55), duration of T2DM (≤1 year: 1; >5-10 years: 1.70, 1.10-2.62; and >10 years: 2.55, 1.68-3.89), and length of hospital stay (≤5 days: 1; >5-10 days: 2.43, 1.86-3.17; and >10 days: 2.99, 2.24-3.99), and were higher in those with poor blood glucose level (2.09, 1.67-2.62) and with comorbidities like other endocrine, nutritional and metabolic diseases (2.24, 1.76-2.85), circulatory system diseases (4.35, 3.62-5.23), skin and subcutaneous tissue diseases (1.64, 1.04-2.59), and musculoskeletal system and connective tissue diseases (1.61, 1.27-2.03). The odds of polypharmacy prescription were lower in those with comorbidities like neoplasms (0.51, 0.36-0.70) and during pregnancy, childbirth and the puerperium (0.06, 0.01-0.49).ConclusionsAround three fourth of T2DM patients at the tertiary care department were prescribed polypharmacy, and the predictors were identified. The study findings could be taken into consideration in future interventional studies aimed at supporting medicines optimisation (and deprescribing) among these patients.

PurposeTo compare and validate the accuracy and ease of use of handheld autorefractors against retinoscopic refraction by an ophthalmologist for assessing the visual acuity of older adults in India.Methods190 patients were enrolled at the Sankara Eye Hospital in Bangalore, India, to undergo refraction using three different handheld devices-Retinomax (Nikon Inc., Japan), Netra (Eyenetra, Inc., USA), and QuickSee (PlenOptika, Inc., USA)-and the results were compared with cycloplegic retinoscopy and refraction done by an ophthalmologist. We analyzed the mean, standard deviation (S.D.), and Bland-Altman comparison of dioptric (D) power accuracy.ResultsThe difference between the handheld devices and subjective refraction for each device was: Retinomax (N = 186), mean -0.41 D, S.D. 2.14; Netra (N = 179), mean 0.61 D, S.D. 2.20; and QuickSee (N = 182), mean -0.05 D, S.D. 1.04.ConclusionThe QuickSee and the Retinomax may be used successfully as refraction screening tools in epidemiologic studies of adults in India and as diagnostic tools in low-resource settings.

PurposeBladder cancer is a "Warburg-like" tumor characterized by a reliance on aerobic glycolysis and expression of pyruvate kinase M2 (PKM2). PKM2 oscillates between an active tetramer and an inactive dimer. We aim to further characterize PKM2, in particular PKM2 dimer, as a urinary biomarker of bladder cancer and a potential target for treatment.MethodsHTB-9, HTB-5, and UM-UC3 bladder cancer cells were assessed for proliferation under differential glucose levels using the hexosaminidase assay. Western blot and Blue-native analysis was performed for protein expression of PKM2. Shikonin, an herb that is known to bind and inhibit PKM2, was utilized to determine if PKM2 has a role in glucose usage and cellular proliferation in bladder cancer cells by caspase activity assay. Institutional review board approval was obtained to collect healthy control and bladder cancer patient urine samples. The ScheBo M2-PK EDTA Plasma Test was performed on urine samples to assess urine Tumor M2-PK values.ResultsThe three bladder cancer cell lines tested all demonstrate statistically significant increases in proliferation when exposed to higher level of glucose (200mg/dL). Similarly, low doses of glucose (25mg/dL) result in reduced proliferation. Increased cell growth in higher glucose concentration correlated with up-regulation of PKM2 protein expression. Shikonin, a PKM2 inhibitor, reduced cell proliferation and switched PKM2 isoforms from the dimer to tetramer. Lastly, dimer PKM2 (Tumor-M2PK) levels were assessed in the urine samples from bladder cancer (Bca) patients and healthy controls. Tumor M2-PK significantly correlated with the presence of BCa in our subjects.ConclusionsOur studies demonstrate the potential of PKM2, specifically the dimer (Tumor-M2PK) as a target of drug therapy and as a urinary marker for bladder cancer.

High-risk human papillomaviruses (hrHPVs) are the most prevalent viruses in human diseases including cervical cancers. Expression of E6 protein has already been reported in cervical cancer cases, excluding normal tissues. Continuous expression of E6 protein is making it ideal to develop therapeutic vaccines against hrHPVs infection and cervical cancer. Therefore, we carried out a meta-analysis of multiple hrHPVs to predict the most potential prophylactic peptide vaccines. In this study, immunoinformatics approach was employed to predict antigenic epitopes of hrHPVs E6 proteins restricted to 12 Human HLAs to aid the development of peptide vaccines against hrHPVs. Conformational B-cell and CTL epitopes were predicted for hrHPVs E6 proteins using ElliPro and NetCTL. The potential of the predicted peptides were tested and validated by using systems biology approach considering experimental concentration. We also investigated the binding interactions of the antigenic CTL epitopes by using docking. The stability of the resulting peptide-MHC I complexes was further studied by molecular dynamics simulations. The simulation results highlighted the regions from 46-62 and 65-76 that could be the first choice for the development of prophylactic peptide vaccines against hrHPVs. To overcome the worldwide distribution, the predicted epitopes restricted to different HLAs could cover most of the vaccination and would help to explore the possibility of these epitopes for adaptive immunotherapy against HPVs infections.

Hawaii has experienced a catastrophic decline in frugivorous native birds coupled with the introduction of non-native species. Puaiohi (Myadestes palmeri), a critically endangered thrush, is the sole extant native songbird capable of dispersing fleshy fruited plants in the rainforest of Kauai island, Hawaii. As this species has declined to occupy a small proportion of its original range, a suite of largely omnivorous non-native birds have been introduced to this region, including the common and widespread Japanese White-eye (Zosterops japonicus). This reshuffling of the bird community could have long-term implications for plant community composition if introduced birds incompletely replace the ecological role of native species. The objective of this study was to evaluate the potential consequences of the local extirpation of Puaiohi for seed dispersal. Specifically, we compared the diet of Puaiohi and Japanese White-eye, vegetation characteristics, and seed rain at sites with and without Puaiohi in the Na Pali-Kona Forest Reserve on the island of Kauai. We found high overlap in the composition of seeds consumed by the two bird species, but differences in the characteristics of seeds consumed; Japanese White-eye appeared more likely to consume smaller seeded species compared with Puaiohi. Sites with Puaiohi received substantially higher seed rain during the study period, despite no significant differences in overall fruit abundance. Our results suggest that non-native birds are unlikely to completely replace the seed dispersal services provided by Puaiohi. If Puaohi continue to be rare and range restricted, we predict a shift in plant community composition through an increase in non-native and small-seeded plants, and possible dispersal failure of other native species. Our findings lend further support to efforts to conserve Puaiohi across its current and former range, and to consider introductions to other suitable areas to ensure the persistence not only of the species and but also its functional role in Hawaii's montane ecosystems.

Leukemia Inhibitory Factor (LIF) is a polyfunctional cytokine, involved in numerous regulatory effects in vivo and in vitro, varying from cell proliferation to differentiation, and has therapeutic potential for treating various diseases. In the current study, a COS-1 cell line overexpressing recombinant Buffalo LIF (rBuLIF) was established. The rBuLIF was purified to homogeneity from the total cell lysate of COS-1 cells using a two-step affinity chromatography. The purified LIF was confirmed by western blot and mass spectrometer (MS/MS). Particularly, high-resolution MS has identified the rBuLIF with 73% of sequence coverage with highest confidence parameters and with the search engine score of 4580. We determined the molecular weight of rBuLIF protein to be 58.99 kDa and 48.9 kDa with and without glycosylation, respectively. Moreover, the purified rBuLIF was verified to be functionally active by measuring the growth inhibition of M1 myeloid leukemia cells, revealing a maximum inhibition at 72 hours and half-maximal effective concentration (EC50) of 0.0555 ng/ml, corresponding to a specific activity of >1.6×10(7) units/mg. Next, we evaluated the effect of rBuLIF on buffalo mammary epithelial cell lines for its role in involution and also identified the IC50 value for BuMEC migrating cells to be 77.8 ng/ml. Additionally, the treatment of MECs (BuMEC and EpH4) displayed significant (P < 0.05) reduction in growth progression, as confirmed by qRT-PCR analysis, suggesting its strong involvement in the involution of the mammary gland in vivo. Thus, we conclude that the glycosylated rBuLIF, purified from COS-1 cells was found to be functionally active as its natural counterpart.

Evaluation and prediction of the performance of hybrids is important in eggplant (Solanum melongena) breeding. A set of 10 morphologically highly diverse eggplant parents, including nine inbred S. melongena and one weedy S. insanum accessions, were intercrossed according to a half-diallel mating design without reciprocals to obtain 45 hybrids. Parents and hybrids were evaluated for 14 morphological and agronomic conventional descriptors and 14 fruit morphometric traits using Tomato Analyzer. Genetic distances among parents were estimated with 7,335 polymorphic SNP markers. Wide ranges of variation and significant differences were observed in the set of 55 genotypes for all traits, although the hybrids group had significantly higher vigour and yield than parents. General and specific combining abilities (GCA and SCA) were significant for most (GCA) or all (SCA) traits, although a wide variation was obtained for GCA/SCA ratios. Many relevant traits associated to vigour and yield had low GCA/SCA ratios and narrow-sense heritability (h2) values, while the reverse occurred for most fruit shape descriptors. Broad-sense heritability (H2) values were generally high, irrespective of GCA/SCA ratios. Significant correlations were found between traits related to size of leaf, flower and fruit, as well as among many fruit morphometric traits. Genetic distances (GD) among parents were coherent with their phylogenetic relationships, but few significant and generally low correlations were found between GD and hybrid means, heterosis or SCA. The results provide relevant information for developing appropriate strategies for parent selection and hybrid development in eggplant and suggest that GD among parents have limited value to predict hybrid performance in this crop.