CT-derived radiomics predict the growth rate of renal tumours in von Hippel-Lindau syndrome.

AIM: To predict renal tumour growth patterns in von Hippel-Lindau syndrome by utilising radiomic features to assist in developing personalised surveillance plans leading to better patient outcomes. MATERIALS AND METHODS: The study evaluated 78 renal tumours in 55 patients with histopathologically-confirmed clear cell renal cell carcinomas (ccRCCs), which were segmented and radiomics were extracted. Volumetric doubling time (VDT) classified the tumours into fast-growing (VDT <365 days) or slow-growing (VDT ≥365 days). Volumetric and diametric growth analyses were compared between the groups. Multiple logistic regression and random forest classifiers were used to select the best features and models based on their correlation and predictability of VDT. RESULTS: Fifty-five patients (mean age 42.2 ± 12.2 years, 27 men) with a mean time difference of 3.8 ± 2 years between the baseline and preoperative scans were studied. Twenty-five tumours were fast-growing (low VDT, i.e., <365 days), and 53 tumours were slow-growing (high VDT, i.e., ≥365 days). The median volumetric and diametric growth rates were 1.71 cm3/year and 0.31 cm/year. The best feature using univariate analysis was wavelet-HLL_glcm_ldmn (area under the receiver operating characteristic [ROC] curve [AUC] of 0.80, p<0.0001), and with the random forest classifier, it was log-sigma-0-5-mm-3D_glszm_ZonePercentage (AUC: 79). The AUC of the ROC curves using multiple logistic regression was 0.74, and with the random forest classifier was 0.73. CONCLUSION: Radiomic features correlated with VDT and were able to predict the growth pattern of renal tumours in patients with VHL syndrome.

Predictive profiling of gram-negative antibiotics in CagA oncoprotein inactivation: a molecular dynamics simulation approach.

Gastric cancer (GC) is the fifth most prevalent form of cancer worldwide. CagA - positive Helicobacter pylori infects more than 60% of the human population. Moreover, chronic infection of CagA-positive H. pylori can directly affect GC incidence. In the current study, we have repurposed FDA-approved antibiotics that are viable alternatives to current regimens and can potentially be used as combination therapy against the CagA of H. pylori. The 100 FDA-approved gram negative antibiotics were screened against CagA protein using the AutoDock 4.2 tool. Further, top nine compounds were selected based on higher binding affinity with CagA. The trajectory analysis of MD simulations reflected that binding of these drugs with CagA stabilizes the system. Nonetheless, atomic density map and principal component analysis also support the notion of stable binding of antibiotics to the protein. The residues ASP96, GLN100, PRO184, and THR185 of compound cefpiramide, doxycycline, delafloxacin, metacycline, oxytetracycline, and ertapenem were involved in the binding with CagA protein. These residues are crucial for the CagA that aids in entry or pathogenesis of the bacterium. The screened FDA-approved antibiotics have a potential druggability to inhibit CagA and reduce the progression of H. pylori borne diseases.

PGPR: the treasure of multifarious beneficial microorganisms for nutrient mobilization, pest biocontrol and plant growth promotion in field crops.

Plant growth-promoting rhizobacteria (PGPR) have multifarious beneficial activities for plant growth promotion; act as source of metabolites, enzymes, nutrient mobilization, biological control of pests, induction of disease resistance vis-a-vis bioremediation potentials by phytoextraction and detoxification of heavy metals, pollutants and pesticides. Agrochemicals and synthetic pesticides are currently being utilized widely in all major field crops, thereby adversely affecting human and animal health, and posing serious threats to the environments. Beneficial microorganisms like PGPR could potentially substitute and supplement the toxic chemicals and pesticides with promising application in organic farming leading to sustainable agriculture practices and bioremediation of heavy metal contaminated sites. Among field crops limited bio-formulations have been prepared till now by utilization of PGPR strains having plant growth promotion, metabolites, enzymes, nutrient mobilization and biocontrol activities. The present review contributes comprehensive description of PGPR applications in field crops including commercial, oilseeds, leguminous and cereal crops to further extend the utilization of these potent groups of beneficial microorganisms so that even higher level of crop productivity and quality produce of field crops could be achieved. PGPR and bacteria based commercialized bio-formulations available worldwide for its application in the field crops have been compiled in this review which can be a substitute for the harmful synthetic chemicals. The current knowledge gap and potential target areas for future research have also been projected.

Global prevalence of edentulism and dental caries in middle-aged and elderly persons: A systematic review and meta-analysis.

OBJECTIVE: The aim of the study was to analyze data collected from studies worldwide on the prevalence of edentulism and dental caries, in community-dwellers aged ≥ 45 years. DATA: Inclusion criteria; participants aged ≥ 45 years, community-dwellers. Exclusion criteria; participants aged < 45 years, in nursing homes, data obtained from dental clinics or pre-2005. The quality assessment tool by The National Heart, Lung and Blood Institute for Observational Cohort and Cross-sectional studies was used. Meta-analysis using the random-effects model (95% confidence interval) was done with data on participants who were edentulous and/or had active dental caries and stratified by regions of the world, age and Gross National Income per capita. Limitations in the data arose from several factors such as design of the studies included differences in socioeconomic status and access to health care among different countries. SOURCES: Embase, MEDLINE via Pubmed and Scopus, manual searches, from January 2016, restricted to English. Experts from different countries were contacted to identify National oral health surveys (NOHS) conducted from 2010 onwards. STUDY SELECTION: Eighty-six papers and seventeen NOHS were selected for data extraction. Majority of the studies (n = 69) were cross-sectional and of fair quality. 1.1%-70%, 4.9% - 98% prevalence of edentulism and dental caries, respectively. 22%, 45% estimated random-effects pooled prevalence of edentulism and dental caries, respectively. CONCLUSIONS: Within the limitations of this study, the findings indicate that untreated dental caries and tooth loss are prevalent on a global level with wide variations among different countries, age groups and socioeconomic status. CLINICAL SIGNIFICANCE: The findings demonstrate the reality of the new cohort of older adults, with higher tooth retention implying more dental caries incidence and the need for different care strategies to ensure better oral health. Large variations and difficulty in making comparisons among different countries highlight the need for more standardized, regular research.

Artificial Intelligence for Caries Detection: Value of Data and Information.

If increasing practitioners' diagnostic accuracy, medical artificial intelligence (AI) may lead to better treatment decisions at lower costs, while uncertainty remains around the resulting cost-effectiveness. In the present study, we assessed how enlarging the data set used for training an AI for caries detection on bitewings affects cost-effectiveness and also determined the value of information by reducing the uncertainty around other input parameters (namely, the costs of AI and the population's caries risk profile). We employed a convolutional neural network and trained it on 10%, 25%, 50%, or 100% of a labeled data set containing 29,011 teeth without and 19,760 teeth with caries lesions stemming from bitewing radiographs. We employed an established health economic modeling and analytical framework to quantify cost-effectiveness and value of information. We adopted a mixed public-private payer perspective in German health care; the health outcome was tooth retention years. A Markov model, allowing to follow posterior teeth over the lifetime of an initially 12-y-old individual, and Monte Carlo microsimulations were employed. With an increasing amount of data used to train the AI sensitivity and specificity increased nonlinearly, increasing the data set from 10% to 25% had the largest impact on accuracy and, consequently, cost-effectiveness. In the base-case scenario, AI was more effective (tooth retention for a mean [2.5%-97.5%] 62.8 [59.2-65.5] y) and less costly (378 [284-499] euros) than dentists without AI (60.4 [55.8-64.4] y; 419 [270-593] euros), with considerable uncertainty. The economic value of reducing the uncertainty around AI's accuracy or costs was limited, while information on the population's risk profile was more relevant. When developing dental AI, informed choices about the data set size may be recommended, and research toward individualized application of AI for caries detection seems warranted to optimize cost-effectiveness.

Comparative study of the anaesthetic efficacy of 4% articaine versus 2% lidocaine with adrenaline during extraction of mandibular molars using an inferior alveolar nerve blocking technique.

Various anaesthetic agents have been used in dentistry for the extraction of teeth. The most commonly used local anaesthetic agent is lidocaine hydrochloride. Recently, articaine hydrochloride came into existence because of its versatile properties and longer duration of action. Due to lack of study of effects of articaine on various systems, the present study is aimed to compare the anaesthetic efficacy of articaine and lidocaine with adrenaline during the extraction of mandibular molars. A total of 100 patients was randomly divided into two groups (50 each) and clinical variables such onset and duration of anaesthesia, blood pressure, oxygen saturation, pulse rate, and pain perception were recorded at different time intervals using a visual analogue scale. The statistical analysis was performed using SPSS version 22.0. Mean and standard deviations, frequency distribution analysis, and the chi squared test were performed to calculate variables and a p< 0.05 was considered significant. Statistically significant differences were obtained regarding mean time of onset of anaesthesia (p< 0.001), mean duration of the anaesthetic effect (p< 0.001), and pain perception for the articaine group. No significant results were obtained for blood pressure, oxygen saturation, or pulse rate. During the deposition of articaine, patients reported less pain than with lidocaine. Articaine hydrochloride helped to achieve increased anaesthetic success in dental applications over lidocaine hydrochloride in terms of fast time of onset, longer duration, and less pain, all of which were attributed to its greater diffusion properties.

Cost-effectiveness of Artificial Intelligence for Proximal Caries Detection.

Artificial intelligence (AI) can assist dentists in image assessment, for example, caries detection. The wider health and cost impact of employing AI for dental diagnostics has not yet been evaluated. We compared the cost-effectiveness of proximal caries detection on bitewing radiographs with versus without AI. U-Net, a fully convolutional neural network, had been trained, validated, and tested on 3,293, 252, and 141 bitewing radiographs, respectively, on which 4 experienced dentists had marked carious lesions (reference test). Lesions were stratified for initial lesions (E1/E2/D1, presumed noncavitated, receiving caries infiltration if detected) and advanced lesions (D2/D3, presumed cavitated, receiving restorative care if detected). A Markov model was used to simulate the consequences of true- and false-positive and true- and false-negative detections, as well as the subsequent decisions over the lifetime of patients. A German mixed-payers perspective was adopted. Our health outcome was tooth retention years. Costs were measured in 2020 euro. Monte-Carlo microsimulations and univariate and probabilistic sensitivity analyses were conducted. The incremental cost-effectiveness ratio (ICER) and the cost-effectiveness acceptability at different willingness-to-pay thresholds were quantified. AI showed an accuracy of 0.80; dentists' mean accuracy was significantly lower at 0.71 (minimum-maximum: 0.61-0.78, P < 0.05). AI was significantly more sensitive than dentists (0.75 vs. 0.36 [0.19-0.65]; P = 0.006), while its specificity was not significantly lower (0.83 vs. 0.91 [0.69-0.98]; P > 0.05). In the base-case scenario, AI was more effective (tooth retention for a mean 64 [2.5%-97.5%: 61-65] y) and less costly (298 [244-367] euro) than assessment without AI (62 [59-64] y; 322 [257-394] euro). The ICER was -13.9 euro/y (i.e., AI saved money at higher effectiveness). In the majority (>77%) of all cases, AI was less costly and more effective. Applying AI for caries detection is likely to be cost-effective, mainly as fewer lesions remain undetected. Notably, this cost-effectiveness requires dentists to manage detected early lesions nonrestoratively.

Perceived susceptibility to developing cancer and mammography screening behaviour: a cross-sectional analysis of Alberta's Tomorrow Project.

OBJECTIVES: Cross-sectional data from Alberta's Tomorrow Project (ATP) were used to assess the association between perceived susceptibility (PS) to developing cancer and mammography screening behaviour. STUDY DESIGN: Cross-sectional study. METHODS: ATP participants between 35 and 70 years of age who reported being free of chronic conditions were included in the study (n = 1803). PS was measured using three variables: participants' estimate of their personal PS of developing cancer, compared to others, on a 5-point Likert scale; participants' estimate of the percentage of people in their age group who would be diagnosed with cancer; and participants' estimate of their own chance (expressed as a percentage) of being diagnosed with cancer. Multivariable logistic regression models, adjusting for age, marital status, work status, education, family history, and place of residence, were used to explore the association of interest. RESULTS: PS of developing cancer was modestly yet significantly associated with mammography screening behaviour for two of the three PS variables. Specifically, the adjusted odds of mammography screening were 1.20 times greater for each one-unit increase in personal PS of developing cancer (95% confidence interval [CI] = 1.07-1.36 [P = 0.003]) and 1.01 times greater for each one-unit increase in both participants' estimate of the percentage of people who would develop cancer (95% CI = 1.00-1.01 [P = 0.05]) and participants' estimate of their own chance of developing cancer (95% CI = 1.00-1.01 [P = 0.02]). CONCLUSIONS: Understanding how certain factors, such as PS, are associated with screening behaviour is important to help address the underutilization of cancer screening.

Actinomycetes: an unexplored microorganisms for plant growth promotion and biocontrol in vegetable crops.

Actinomycetes, a Gram positive bacteria, well reported as a source of antibiotics, also possess potential to control various plant pathogens, besides acting as plant growth promoting agent. Chemicals in different forms are extensively being used in vegetable farming, adversely affecting the environment and consumer health. Microbial agent like actinomycetes can substantially replace these harmful chemicals, and have now started finding a place as an important input in to farming practices. Only selected vegetable crops belonging to 11 different families have been explored with use of actinomycetes as biocontrol and plant growth promoting agent till now. It provides ample opportunities to vegetable researchers, to further explore with use of this very important group of microorganisms, in order to achieve even higher production level of safe vegetables. Mycostop and Actinovate are two actinomycetes based formulations globally available for use in vegetable farming as a substitute for chemical formulations. Present review article has summarized the literature available on use of actinomycetes in vegetable farming. Existing wide gap in knowledge, and potential thrust areas for future research have also been projected.

The inheritance of juvenile onset primary open angle glaucoma.

Juvenile onset open angle glaucoma (JOAG) affects patients before 40 years of age, who present with high intraocular pressure and deep steep cupping of the optic nerve head. While it was considered to be inherited in an autosomal dominant fashion, recent studies have shown an autosomal recessive pattern as well as sporadic occurrence of the disease in several families. In this review, we analyze the genetic basis of the disease along with common mutations and their association with JOAG. We also analyzed the inheritance patterns in a large group of unrelated JOAG patients (n = 336) from Northern India wherein the prevalence of familial occurrence was assessed and segregation analysis performed, to determine the mode of inheritance.

Synthesis, characterization and biocompatibility of chitosan functionalized superparamagnetic nanoparticles for heat activated curing of cancer cells.

Surface functionalization, colloidal stability and biocompatibility of magnetic nanoparticles are crucial for their biological applications. Here, we report a synthetic approach for the direct preparation of superparamagnetic nanoparticles consisting of a perovskite LSMO core modified with a covalently linked chitosan shell that provides colloidal stability in aqueous solutions for cancer hyperthermia therapy. The characterization of the core-shell nanostructure using Fourier transform infrared spectroscopy; thermo-gravimetric analysis to assess the chemical bonding of chitosan to nanoparticles; field-emission scanning electron microscopy and transmission electron microscopy for its size and coating efficiency estimation; and magnetic measurement for their magnetization properties was performed. Zeta potential and light scattering studies of the core shell revealed it to possess good colloidal stability. Confocal microscopy and MTT assay are performed for qualitative and quantitative measurement of cell viability and biocompatibility. In depth cell morphology and biocompatibility is evaluated by using multiple-staining of different dyes. The magnetic@chitosan nanostructure system is found to be biocompatible up to 48 h with 80% cell viability. Finally, an in vitro cancer hyperthermia study is done on the MCF7 cell line. During in vitro hyperthermia treatment of cancer cells, cell viability is reduced upto 40% within 120 min with chitosan coated nanoparticles. Our results demonstrate that this simplified and facile synthesis strategy shows potential for designing a colloidal stable state and biocompatible core shell nanostructures for cancer hyperthermia therapy.

Technetium-99m-labeled deoxynivalenol from Fusarium mycotoxin alters organ toxicity in BALB/c mice by oral and intravenous route

The toxicity of deoxynivalenol, both intravenously and orally, was investigated in male and female BALB/c mice. Technetium-99m (99m Tc)-labeled deoxynivalenol was administered to mice by tail vein injection and orally dosed. Distribution of labeled deoxynivalenol at 26 hours was monitored by gamma-scintigraphy. In the evaluated organs, the accumulation of radioactive deoxynivalenol was correlated with the amount of radioactivity. In addition, the toxicity of deoxynivalenol was measured by biochemical assays followed by histopathological findings. Kidney and hepatic marker enzymes were significantly increased in intravenously administered deoxynivalenol as compared to orally treated mice. Intravenously treated mice showed severe damage in liver and kidney when compared to those orally exposed. Biodistribution of 99mTc-labeled deoxynivalenol differed between oral and intravenous treatment. In intravenously exposed mice, deoxynivalenol was distributed primarily in the liver and kidney whereas in oral exposure, it was found in the stomach and intestines after 26 hours. Deoxynivalenol toxicity, associated with its biodistribution and organ toxicity, was greatest where it had accumulated. The results show that the toxicity of deoxynivalenol is associated with organ accumulation.(AU)

Anti-inflammatory, analgesic and antipyretic activities of Linum usitatissimum L. (flaxseed/linseed) fixed oil.

The fixed oil of L. usitatissimum (flaxseed/linseed) inhibited PGE2-, leukotriene-, histamine- and bradykinin-induced inflammation. The oil also inhibited arachidonic acid-induced inflammation, suggesting its capacity to inhibit both cyclooxygenase and lipoxygenase pathways of arachidonate metabolism. In tail immersion model, the oil raised the pain threshold to a lesser extent than morphine but showed excellent peripherally acting, analgesic activity comparable to aspirin, against acetic acid-induced writhing in mouse. In typhoid paratyphoid A/B vaccine-induced pyrexia, the oil showed antipyretic activity comparable to aspirin. The oil contains 57.38% alpha-linolenic acid. Dual inhibition of arachidonic acid metabolism, antihistaminic and antibradykinin activities of the oil could account for the biological activity and the active principle could be alpha-linolenic acid an omega-3 (18:3, n-3) fatty acid.

Central neurocytoma in the vermis of the cerebellum.

In neuropathology, anatomic landmarks and topographic relationships bear particularly on issues of differential diagnosis. A case of central neurocytoma of the vermis of the cerebellum is being reported in this article. A 45-year-old male with features of hydrocephalous and a posterior fossa space-occupying lesion was diagnosed as having central neurocytoma upon a microscopy of Hematoxylene and Eosin stained sections. The diagnosis was confirmed by a positive immunohistochemical reaction for Neuron Specific Enolase (NSE) and Synaptophysin. This case report is being made to emphasize that a high index of suspicion is required even for reporting neuropathology where the site does not match the conventional location of the lesion seen and also to emphasize the importance of immunohistochemistry in proving such unusually located lesions.

RAPD based genetic variability among cultivated varieties of Aonla (Indian Gooseberry, Phyllanthus emblica L.).

Aonla, the Indian Gooseberry (Phyllanthus emblica) is widely grown in India due to its neutraceutical properties. Investigations on the use of RAPD markers enabled us to estimate genetic variability among commercially cultivated varieties. This study also enabled us to distinguish these varieties using a set of four decamer primers, which was otherwise difficult by using morphological markers. Cluster analysis revealed three different groups of varieties directly associated to their place of origin. RAPD markers were also able to differentiate varieties of same origin or even selection from same parents. This information can be used for identification of varieties and further crop improvement programme.