Number Of Human Illnesses Research Articles

IDLB-Pred: identification of disordered lipid binding residues in protein sequences using convolutional neural network

Proteins, nucleic acids, and lipids all interact with intrinsically disordered protein areas. Lipid-binding regions are involved in a variety of biological processes as well as a number of human illnesses. The expanding body of experimental evidence for these interactions and the dearth of techniques to anticipate them from the protein sequence serve as driving forces. Although large-scale laboratory techniques are considered to be essential for equipment for studying binding residues, they are time consuming and costly, making it challenging for researchers to predict lipid binding residues. As a result, computational techniques are being looked at as a different strategy to overcome this difficulty. To predict disordered lipid-binding residues (DLBRs), we proposed iDLB-Pred predictor utilizing benchmark dataset to compute feature through extraction techniques to identify relevant patterns and information. Various classification techniques, including deep learning methods such as Convolutional Neural Networks (CNNs), Deep Neural Networks (DNNs), Multilayer Perceptrons (MLPs), Recurrent Neural Networks (RNNs), Long Short-Term Memory (LSTM) networks, and Gated Recurrent Units (GRUs), were employed for model training. The proposed model, iDLB-Pred, was rigorously validated using metrics such as accuracy, sensitivity, specificity, and Matthew’s correlation coefficient. The results demonstrate the predictor’s exceptional performance, achieving accuracy rates of 81% on an independent dataset and 86% in 10-fold cross-validation.

Evaluation of Cyto-Genotoxicity of Pharmaceutical Industrial Effluent in Kano Metropolis, Kano State, Nigeria, Using Allium Cepa L. Assay

ABSTRACT
 An Allium cepa root cells assay was used to assess cytotoxic and genotoxic impacts on Pharmaceutical industrial effluent in Kano Metropolis. An industrial effluent's physicochemical characteristics and heavy metal composition were assessed, and the readings were found to be higher than the required levels, demonstrating that it had not been treated before disposal. A set of 45 onion bulbs were grown for 96 hours in pharmaceutical effluent that included 2.5, 5.0, 7.5, and 10.0% (v/v), with distilled water serving as the control. All three root tips from each replication's treated bulbs were plucked at 96 hours and prepared for cytogenetic analysis using the aceto-carmine squashed procedure. At higher doses of industrial effluents, the root tips were highly cytotoxic, and their growth was strongly retarded. Exposure to the effluents inhibited root growth with an EC50 value of 6.3%. An analysis of variance (ANOVA) revealed a significant difference (P 0.05) in the average root growth of Allium cepa subjected to various pharmaceutical effluent concentrations. Mitosis Index (MI) rapidly reduced when effluent concentrations rose compared to control, whereas mitotic inhibition rose with rising effluent concentrations compared to controls. The pharmaceutical effluent triggered chromosomal abnormalities in Allium cepa root tip cells, particularly sticky chromosomes, Binucleated cells, and Bridge chromosomes being most commonly seen at lower doses of 2.5%. It was discovered that the compounds present in effluent might harm living things and, if left untreated, could poison the environment. Industrialists need to be legally required to switch their operations to environmentally friendly technology after it was determined that industrial effluents pose an environmental danger and can result in a number of human illnesses.

SUGARCANE JUICE AS A POTENTIAL SOURCE OF ANTIBIOTIC RESISTANT SALMONELLA SPP.

Many segments of the population now get affordable foods because of growing trend of street vending in developing nations. There have been reports from all over the world that fruit juices sold on streets are tainted with numerous bacteria causing a number of human illnesses. Major outbreaks brought on by microbial pathogens of fruit juices have resulted in severe illness and mortality in underdeveloped nations. This study determine the prevalence of antibiotic resistant Salmonella spp. in sugarcane juice samples available from street vendors in Shahadara Lahore. Ten sugarcane juice samples were bought from different street vendors. Microbiological assess-ment tests were performed on each sample. Salmonella Shigella (SS) and MacConkey agar ere used as the media from the growth of bacteria. To check the resistance of Salmonella of four antibiotics were used. When compared to the advised standard safety practices, the findings showed that the majority of the suppliers did not adhere to cleanliness and safety practices. On SS and MacConkey agar highest contamination was found to be 2.45×10^5 and 7.8×10^5 Salmonella cfu per serving of sample, respectively. Highest antibiotic resistance was found against cefotaxime as 7.5×10^4 cfu per serving of sample in SJS10. Microbiological quality of sugarcane juices fell beyond permissible ranges, possibly as a result of the poor water quality used to make the juices as well as the sellers' poor hygiene and safety procedures. The isolated microorganisms were ciprofloxacin and cefotaxime resistant, which could have serious effects on public health. The research on antibiotic resistant bacteria in sugarcane juices had not been done before from this region has added fresh knowledge to the field's domain of research

Src family kinases Fyn and Lyn are constitutively activated and mediate plasmacytoid dendritic cell responses

Plasmacytoid dendritic cells (pDC) are type I interferon-producing cells with critical functions in a number of human illnesses; however, their molecular regulation is incompletely understood. Here we show the role of Src family kinases (SFK) in mouse and human pDCs. pDCs express Fyn and Lyn and their activating residues are phosphorylated both before and after Toll-like receptor (TLR) stimulation. Fyn or Lyn genetic ablation as well as treatment with SFK inhibitors ablate pDC (but not conventional DC) responses both in vitro and in vivo. Inhibition of SFK activity not only alters TLR-ligand localization and inhibits downstream signalling events, but, independent of ex-vivo TLR stimulation, also affects constitutive phosphorylation of BCAP, an adaptor protein bridging PI3K and TLR pathways. Our data identify Fyn and Lyn as important factors that promote pDC responses, describe the mechanisms involved and highlight a tonic SFK-mediated signalling that precedes pathogen encounter, raising the possibility that small molecules targeting SFKs could modulate pDC responses in human diseases.

Salmonella and Campylobacter baseline in retail ground beef and whole-muscle cuts purchased during 2010 in the United States.

Salmonella enterica and Campylobacter spp. cause a considerable number of human illnesses each year, and the vast majority of cases are foodborne. The purpose of this study was to establish the baseline of Salmonella and Campylobacter in beef products purchased from U.S. retail markets. Sampling was carried out in 38 American cities. Retail raw ground and whole-muscle beef (n = 2,885) samples were purchased and examined for the presence of Salmonella. Samples testing positive for Salmonella were identified with the commercial BAX System, which is a real-time PCR-based system. Of the original samples purchased, 1,185 were selected and tested for the presence of Campylobacter. Positive samples were isolated via direct plating and confirmed via agglutination and biochemical testing. Salmonella was detected in 0.66% of the total samples purchased. The prevalence of Salmonella in ground beef packages was 0.42% for modified atmosphere packaging, 0.63% for chub packaging, and 0.59% for overwrapped packages. Salmonella was detected in 1.02% of whole-muscle cuts. There was no relationship (P = 0.18) between product type (ground or whole muscle) and the percentage of positive samples. Campylobacter was recovered from 9.3% of samples. A greater percentage (17.24%, P < 0.01) of whole-muscle cuts tested positive for Campylobacter compared with ground beef samples (7.35%). Estimating pathogen baselines in U.S. retail beef is essential for allotting resources and directing interventions for pathogen control. These data can be utilized for a more complete understanding of these pathogens and their impact on public health from the consumption of beef products.

Framework for Microbial Food‐Safety Risk Assessments Amenable to Bayesian Modeling

Regulatory agencies often perform microbial risk assessments to evaluate the change in the number of human illnesses as the result of a new policy that reduces the level of contamination in the food supply. These agencies generally have regulatory authority over the production and retail sectors of the farm-to-table continuum. Any predicted change in contamination that results from new policy that regulates production practices occurs many steps prior to consumption of the product. This study proposes a framework for conducting microbial food-safety risk assessments; this framework can be used to quantitatively assess the annual effects of national regulatory policies. Advantages of the framework are that estimates of human illnesses are consistent with national disease surveillance data (which are usually summarized on an annual basis) and some of the modeling steps that occur between production and consumption can be collapsed or eliminated. The framework leads to probabilistic models that include uncertainty and variability in critical input parameters; these models can be solved using a number of different Bayesian methods. The Bayesian synthesis method performs well for this application and generates posterior distributions of parameters that are relevant to assessing the effect of implementing a new policy. An example, based on Campylobacter and chicken, estimates the annual number of illnesses avoided by a hypothetical policy; this output could be used to assess the economic benefits of a new policy. Empirical validation of the policy effect is also examined by estimating the annual change in the numbers of illnesses observed via disease surveillance systems.

Everolimus (RAD001) in the treatment of advanced renal cell carcinoma: biology and pathways

Everolimus (RAD001) is an orally administered inhibitor of the mammalian target of rapamycin (mTOR), an intracellular serine/threonine kinase that regulates protein synthesis and cell growth, proliferation and survival. Dysfunction of mTOR has been implicated in a number of human illnesses including cancer and everolimus is used for a variety of therapeutic indications and is under evaluation in clinical trials for the treatment of cancer. Two phase I studies evaluating the dosing, toxicity, pharmacokinetics, pharmacodynamics and potential biomarkers of everolimus in advanced cancer have been reported. Daily doses of 10 mg and weekly doses of 50 mg of everolimus appear to inhibit relevant therapeutic targets in both tumour tissue and in skin but maximum-tolerated doses of everolimus were not determined formally in these studies. A phase III study of everolimus at 10 mg daily in the treatment of patients with advanced renal cell carcinoma who had failed prior treatment with sorafenib or sunitinib has also been reported. In this study everolimus was generally well tolerated, causing rash, stomatitis and fatigue in approximately a third of patients which generally were not severe. Hyperglycaemia, hypertriglyceridaemia and hypercholesterolaemia were reported in approximately two-thirds of patients but again were easy to manage and mainly of mild or moderate severity. Severe infections and non-infectious pneumonitis were reported in less than 5% of study participants but generally responded to standard therapies. Further work is necessary to define mechanisms of activity and toxicity of everolimus in the treatment of advanced renal cell carcinoma.

Negative Regulation of NF-κB Signaling by PIAS1

The NF-kappaB family of transcription factors is activated by a wide variety of signals to regulate a spectrum of cellular processes. The proper regulation of NF-kappaB activity is critical, since abnormal NF-kappaB signaling is associated with a number of human illnesses, such as chronic inflammatory diseases and cancer. We report here that PIAS1 (protein inhibitor of activated STAT1) is an important negative regulator of NF-kappaB. Upon cytokine stimulation, the p65 subunit of NF-kappaB translocates into the nucleus, where it interacts with PIAS1. The binding of PIAS1 to p65 inhibits cytokine-induced NF-kappaB-dependent gene activation. PIAS1 blocks the DNA binding activity of p65 both in vitro and in vivo. Consistently, chromatin immunoprecipitation assays indicate that the binding of p65 to the promoters of NF-kappaB-regulated genes is significantly enhanced in Pias1-/- cells. Microarray analysis indicates that the removal of PIAS1 results in an increased expression of a subset of NF-kappaB-mediated genes in response to tumor necrosis factor alpha and lipopolysaccharide. Consistently, Pias1 null mice showed elevated proinflammatory cytokines. Our results identify PIAS1 as a novel negative regulator of NF-kappaB.

An overview of the Salmonella enteritidis risk assessment for shell eggs and egg products.

This article summarizes a quantitative microbial risk assessment designed to characterize the public health impact of consumption of shell eggs and egg products contaminated with Salmonella Enteritidis (SE). This risk assessment's objectives were to: (1) establish the baseline risk of foodborne illness from SE, (2) identify and evaluate potential risk mitigation strategies, and (3) identify data gaps related to future research efforts. The risk assessment model has five modules. The Egg Production module estimates the number of eggs produced that are SE-contaminated. Shell Egg Processing, Egg Products Processing, and Preparation & Consumption modules estimate the increase or decrease in the numbers of SE organisms in eggs or egg products as they pass through storage, transportation, processing, and preparation. A Public Health Outcomes module then calculates the incidence of illnesses and four clinical outcomes, as well as the cases of reactive arthritis associated with SE infection following consumption. The baseline model estimates an average production of 2.3 million SE-contaminated shell eggs/year of the estimated 69 billion produced annually and predicts an average of 661,633, human illnesses per year from consumption of these eggs. The model estimates approximately 94% of these cases recover without medical care, 5% visit a physician, an additional 0.5% are hospitalized, and 0.05% result in death. The contribution of SE from commercially pasteurized egg products was estimated to be negligible. Five mitigation scenarios were selected for comparison of their individual and combined effects on the number of human illnesses. Results suggest that mitigation in only one segment of the farm-to-table continuum will be less effective than several applied in different segments. Key data gaps and areas for future research include the epidemiology of SE on farms, the bacteriology of SE in eggs, human behavior in food handling and preparation, and human responses to SE exposure.

Waterborne adenovirus: a risk assessment

Adenoviruses have been detected in raw sewage throughout the world and are associated with a number of human illnesses but their occurrence and pathogenicity have not been well studied. A risk assessment approach was used to determine their significance as a waterborne pathogen. There are 47 types of adenoviruses and the diseases resulting from infections include conjunctivitis, pharyngitis, pneumonia, acute and chronic appendicitis, exanthematous disease, bronchiolitis, acute respiratory disease, and gastroenteritis (types 40 and 41). Adenovirus is considered to be only second to rotavirus in terms of its significance as a pathogen of childhood gastroenteritis. Adenovirus infections are usually acute and self-limiting with a greater severity of illness occurring in the immunocompromised (e.g. AIDS patients and transplant recipients). They are reported to be more resistant to inactivation by UV than enteroviruses and are sometimes detected at higher levels in polluted waters. There are documented outbreaks of conjunctivitis due to adenovirus types 3 &amp; 4 associated with swimming in contaminated recreational waters. Based on the data obtained from human dose-response studies, the exponential model [Pi = 1 -exp(-rN); r = 0.4172] was chosen for this risk assessment. Annual risks of infection in drinking water for adenovirus at average levels of 1/1,000L to 1/100L ranged from 8.3/10,000 to 8.3/1,000, respectively. Using monitoring data from a recreational water, risks were calculated to be as high as 1/1,000 for a single exposure.

Waterborne adenovirus: A risk assessment

Adenoviruses have been detected in raw sewage throughout the world and are associated with a number ofhuman illnesses but their occurrence and pathogenicity have not been well studied. A risk assessment approach was used to determine their significance as a waterborne pathogen. There arc 47 types of adenoviruses and the diseases resulting from infections include conjunctivitis, pharyngitis, pneumonia, acute and chronic appendicitis, cxanthematous disease, bronchiolitis, acute respiratory disease, and gastroenteritis (types 40 and 41). Adenovirus is considered to be only second to rolavirus in terms of its significance as a pathogen of childhood gastroenteritis. Adenovirus infections are usually acute and self-limiting with a greater severity of illness occurring in the immunocompromised (e.g. AIDS patients and transplant recipients). They are repofled to be more resistant to inactivation by UV than enteroviruses and are sometimes detected at higher levels in polluted waters. There are documented outbreaks of conjunctivitis due to adenovirus types 3 & 4 associated with swimming in contaminated recreational waters. Based on the data obtained from human dose-response studies, the exponential model [Pi = l -exp(-rN); r = 0.4172] was chosen for this risk assessment. Annual risks of infection in drinking water for adenovirus at average levels of 1/1,000L to 1/100L ranged from 8.3/10,000 to 8.3/1,000, respectively. Using monitoring data from a recreational water, risks were calculated to be as high as 1/1,000 for a single exposure.

Effects of hyperammonemia on brain protein kinase C substrates.

Ammonia is a product of the degradation of proteins and of other compounds ; however, when it is in excess, ammonia is a toxic compound . A fiveto ten-fold increase in blood ammonia levels leads to alterations in the function of the central nervous system, and can lead to coma and death . To prevent these toxic effects, ureotelic animals have developed the urea cycle, which is mainly located in liver, and eliminates ammonia by incorporating it into urea, which is eliminated in urine . This maintains safe levels of ammonia in blood and tissues. However, when this process fails due to a congenital defect in the urea cycle enzymes or by impairment of liver function, the levels of ammonia in blood rise and can lead to altered brain function. This syndrome, known as hepatic encephalopathy, can lead to coma and death. Ammonia interferes with neurotransmission and with electrophysiological processes (Fan et al., 1990; Szerb and Butterworth, 1992 ; Raabe and Lin, 1984 ; Raabe, 1992 and 1994, Butterworth, 1994) . There are a number of human illnesses that are associated with increased levels of ammonia in blood, including liver cirrhosis, fulminant hepatic failure and congenital defects of urea cycle enzymes . Independently of its origin, in these situations the levels of ammonia in blood increase 5 to 10-fold, leading to hepatic encephalopathy, and high mortality . In fact, hepatic encephalopathy is one of the main causes of death in occidental countries . In Spain 12,000 people die every year for this reason, which represents about

Exogenously-induced, natural killer cell-mediated neuronal killing: a novel pathogenetic mechanism.

Many human neurodegenerative diseases are characterized by the idiopathic death of cells narrowly restricted to a subset of neurons in a specific functional neuroanatomic system. Few in vivo models exist for the analysis of these types of degeneration. This report documents the death of sympathetic neurons resident in the superior cervical ganglia of rats after exposure to an exogenous chemical agent, the drug guanethidine, as being mediated by natural killer (NK) cells. This is the first in vivo model of a disorder of the nervous system in which NK cells appear to be the principal effector cell, and thus could serve a central role in dissecting the normal and pathological function of NK cells. In addition, this pathogenetic mechanism appears to represent a novel type of autoimmune reaction that could have a direct bearing on a number of human illnesses.