Search results for: benign breast disease

Authors: Dulal Bhaumik, Fei Jie, Runa Bhaumik, Bikas Sinha

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Human brain is an amazingly complex network. Aberrant activities in this network can lead to various neurological disorders such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease and autism. fMRI has emerged as an important tool to delineate the neural networks affected by such diseases, particularly autism. In this paper, we propose mixed-effects models together with an appropriate procedure for controlling false discoveries to detect disrupted connectivities in whole brain studies. Results are illustrated with a large data set known as Autism Brain Imaging Data Exchange or ABIDE which includes 361 subjects from 8 medical centers. We believe that our findings have addressed adequately the small sample inference problem, and thus are more reliable for therapeutic target for intervention. In addition, our result can be used for early detection of subjects who are at high risk of developing neurological disorders.

Keywords: ABIDE, autism spectrum disorder, fMRI, mixed-effects model

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Authors: Anthara Vivek, Manisha Shukla, Mahesh Narayan, Prakash Narayan

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Sickle cell disease disproportionately affects sub-Saharan Africa and certain tribal populaces in India and has consequently drawn little intertest from Pharma. In sickle cell patients, adhesion of erythrocytes or reticulocytes to one another and the vessel wall results in painful ischemic episodes with few, if any, effective treatments for vaso-occlusive crises. Identification of disease-associated adhesion markers on erythrocytes or reticulocytes might inform the use of more effective therapies against vaso-occlusive crises. Increased expression of one or more of bcam, itga4, cd44, cd47, rap1a, vcam1, or icam4 has been reported in sickle cell subjects. Using the miRNet ontology knowledgebase, peripheral blood interactomes were generated by seeding various combinations of the afore-referenced mRNA. These interactomes yielded an array of miR targets. As examples, targeting hsa-miR-155-5p can potentially neutralize the rap1a-bcam-cd44-itga4-vcam1 erythrocyte/reticulocyte adhesion interactome whereas targeting hsa-miRs-103a-3p or 107 can potentially neutralize adhesion in cells overexpressing icam4-cd47-bcam-itga4-cd36. AM3380 (MIRacle™) is an off-the shelf hsa-miR-155-5p agomiR that can potentially neutralize the rap1a-bcam-cd44-itga4-vcam1 signaling axis. Phlebotomy coupled with transcriptomics represents a potentially feasible and effective precision medicine strategy to mitigate vaso-occlusive crises in sickle cell patients.

Keywords: adhesion, interactome, precision, medicine

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Authors: K. H. Reeta, Bhavana Prasher, Mitali Mukerji, Dhwani Dholakia, Sangeeta Khanna, Archana Vats, Shivam Pandey, Sandeep Seth, Subir Kumar Maulik

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Introduction Research has demonstrated a connection between coronary artery disease (CAD) and genetics. We did a deep literature mining using both bioinformatics and manual efforts to identify the susceptible polymorphisms in coronary artery disease. Further, the study sought to validate these findings in an Asian population. Methodology In first phase, we used an automated pipeline which organizes and presents structured information on SNPs, Population and Diseases. The information was obtained by applying Natural Language Processing (NLP) techniques to approximately 28 million PubMed abstracts. To accomplish this, we utilized Python scripts to extract and curate disease-related data, filter out false positives, and categorize them into 24 hierarchical groups using named Entity Recognition (NER) algorithms. From the extensive research conducted, a total of 466 unique PubMed Identifiers (PMIDs) and 694 Single Nucleotide Polymorphisms (SNPs) related to coronary artery disease (CAD) were identified. To refine the selection process, a thorough manual examination of all the studies was carried out. Specifically, SNPs that demonstrated susceptibility to CAD and exhibited a positive Odds Ratio (OR) were selected, and a final pool of 324 SNPs was compiled. The next phase involved validating the identified SNPs in DNA samples of 96 CAD patients and 37 healthy controls from Indian population using Global Screening Array. ResultsThe results exhibited out of 324, only 108 SNPs were expressed, further 4 SNPs showed significant difference of minor allele frequency in cases and controls. These were rs187238 of IL-18 gene, rs731236 of VDR gene, rs11556218 of IL16 gene and rs5882 of CETP gene. Prior researches have reported association of these SNPs with various pathways like endothelial damage, susceptibility of vitamin D receptor (VDR) polymorphisms, and reduction of HDL-cholesterol levels, ultimately leading to the development of CAD. Among these, only rs731236 had been studied in Indian population and that too in diabetes and vitamin D deficiency. For the first time, these SNPs were reported to be associated with CAD in Indian population. Conclusion: This pool of 324 SNP s is a unique kind of resource that can help to uncover risk associations in CAD. Here, we validated in Indian population. Further, validation in different populations may offer valuable insights and contribute to the development of a screening tool and may help in enabling the implementation of primary prevention strategies targeted at the vulnerable population.

Keywords: coronary artery disease, single nucleotide polymorphism, susceptible SNP, bioinformatics

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Authors: Mahdi Farajzadeh Ajirlou

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The detailed serious adverse effects raised the stresses around the safety of individuals who have gotten COVID-19 vaccines. Numerous verification referrers that disease with COV-19 causes neurological dysfunction in a significant proportion of influenced patients, where these side effects show up seriously amid the disease, and still less is known approximately the potential long-term results for the brain, where the loss of olfaction could be a neurological sign and simple indications of COVID-19. Since publishing effective clinical trial results of mRNA coronavirus disease 2019 (COVID-19) and injecting it to the volunteers in 2020, numerous reports have emerged approximately about cardiovascular complications followed by the mRNA vaccination. Vaccination-associated adenopathy could be a constant imaging finding after the organization of COVID-19 antibodies that will lead to a symptomatic problem in patients with shown or suspected cancer, in whom it may be vague from dangerous nodal inclusion. In spite of all the benefits and viability of the coronavirus infection 2019 (COVID-19) antibodies specified in later clinical trials, a few other post-vaccination side impacts, such as lymphadenopathy (LAP), were observed. Also, numerous variables, including financial conditions, have played a critical part in expanding the number of people with COVID-19 infection and also much more side effects in that country. Amid the Coronavirus widespread, Iran has been experiencing extreme sanctions, which has faced this nation with an extreme financial crisis. Additionally, with COVID-19 widespread, there was a developing concern around the abuse of imaging exams extraordinarily within the pediatric populace, which highlights the issues pointed out by this review.

Keywords: radiology, vaccines, COVID-19, side effect

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Authors: Tahir Majeed, Michael Handschuh, René Meier

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Rheumatoid arthritis patients have swelling and pain at the joints of the hand. The regions where the patient feels pain also show increased body temperature. Thermal cameras can be used to detect the rise in temperature of the affected regions. To monitor the disease progression of rheumatoid arthritis patients, they must visit the clinic regularly for scanning and examination. After scanning and evaluation, the dosage of the medicine is regulated accordingly. To monitor the disease progression over time, the correlation between the images between different visits must be established. It has been observed that by using low-cost thermal cameras, the thermal measurements do not remain the same over time, even within a single scanning. In some situations, temperatures can vary as much as 2°C within the same scanning sequence. In this paper, it has been shown that although the absolute temperature varies over time, the relative difference between the different regions remains similar. Results have been computed over four scanning sequences and are presented.

Keywords: relative thermal difference, rheumatoid arthritis, thermal imaging, thermal sensors

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Authors: Salam N. Abdo, Orien L. Tulp, George P. Einstein

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The purpose of this exploratory study was to gather the insights into psoriasis etiology, treatment, and patient experience, for developing psoriasis and psoriatic arthritis diagnostic test. Data collection methods consisted of a comprehensive meta-analysis of relevant studies and psoriasis patient survey. Established meta-analysis guidelines were used for the selection and qualitative comparative analysis of psoriasis and psoriatic arthritis research studies. Only studies that clearly discussed psoriasis etiology, treatment, and patient experience were reviewed and analyzed, to establish a qualitative data base for the study. Using the insights gained from meta-analysis, an existing psoriasis patient survey was modified and administered to collect additional data as well as triangulate the results. The hypothesis is that specific types of psoriatic disease have specific etiology and pathophysiologic pattern. The following etiology categories were identified: bacterial, environmental/microbial, genetic, immune, infectious, trauma/stress, and viral. Additional results, obtained from meta-analysis and confirmed by patient survey, were the common age of onset (early to mid-20s) and type of psoriasis (plaque; mild; symmetrical; scalp, chest, and extremities, specifically elbows and knees). Almost 70% of patients reported no prescription drug use due to severe side effects and prohibitive cost. These results will guide the development of psoriasis and psoriatic arthritis diagnostic test. The significant number of medical publications classified psoriatic arthritis disease as inflammatory of an unknown etiology. Thus numerous meta-analyses struggle to report any meaningful conclusions since no definitive results have been reported to date. Therefore, return to the basics is an essential step to any future meaningful results. To date, medical literature supports the fact that psoriatic disease in its current classification could be misidentifying subcategories, which in turn hinders the success of studies conducted to date. Moreover, there has been an enormous commercial support to pursue various immune-modulation therapies, thus following a narrow hypothesis/mechanism of action that is yet to yield resolution of disease state. Recurrence and complications may be considered unacceptable in a significant number of these studies. The aim of the ongoing study is to focus on a narrow subgroup of patient population, as identified by this exploratory study via meta-analysis and patient survey, and conduct an exhaustive work up, aiming at mechanism of action and causality before proposing a cure or therapeutic modality. Remission in psoriasis has been achieved and documented in medical literature, such as immune-modulation, phototherapy, various over-the-counter agents, including salts and tar. However, there is no psoriasis and psoriatic arthritis diagnostic test to date, to guide the diagnosis and treatment of this debilitating and, thus far, incurable disease. Because psoriasis affects approximately 2% of population, the results of this study may affect the treatment and improve the quality of life of a significant number of psoriasis patients, potentially millions of patients in the United States alone and many more millions worldwide.

Keywords: biologics, early diagnosis, etiology, immune disease, immune modulation therapy, inflammation skin disorder, phototherapy, plaque psoriasis, psoriasis, psoriasis classification, psoriasis disease marker, psoriasis diagnostic test, psoriasis marker, psoriasis mechanism of action, psoriasis treatment, psoriatic arthritis, psoriatic disease, psoriatic disease marker, psoriatic patient experience, psoriatic patient quality of life, remission, salt therapy, targeted immune therapy

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Authors: Manik Sharma

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Understanding the anatomy and normal anatomical variations of the lower limb arterial system is undeniably important not only to understand the pathology involving the vessels of the lower limb but also as a part of endovascular intervention and surgical planning in cases that demand them as a part of treatment. There have been very few cases of duplication of SFA cited in the literature, close to six worldwide and this being the seventh case in the world and first to be reported in the Indian population. We incidentally came across this normal variant during US lower limb (US-LL) duplex scan in a patient with claudicating pain in bilateral lower limbs hence suspected of having peripheral vascular disease. It was confirmed on CT-Peripheral Angiography (CT-PA), which was done successively.

Keywords: peripheral vascular disease, claudicating pain, normal anatomical variants, endovascular intervention, duplication, CT-peripheral angiography, duplex scan, Iohexol

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Authors: Delele Worku Ayele, Bing-Joe Hwang

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A method that does not employ hot injection techniques has been developed for the size-tunable synthesis of high-quality CdSe quantum dots (QDs) with a zinc blende structure. In this environmentally benign synthetic route, which uses relatively less toxic precursors, solvents, and capping ligands, CdSe QDs that absorb visible light are obtained. The size of the as-prepared CdSe QDs and, thus, their optical properties can be manipulated by changing the microwave reaction conditions. The QDs are characterized by XRD, TEM, UV-vis, FTIR, time-resolved fluorescence spectroscopy, and fluorescence spectrophotometry. In this approach, the reaction is conducted in open air and at a much lower temperature than in hot injection techniques. The use of microwaves in this process allows for a highly reproducible and effective synthesis protocol that is fully adaptable for mass production and can be easily employed to synthesize a variety of semiconductor QDs with the desired properties. The possible application of the as-prepared CdSe QDs has been also assessed using deposition on TiO2 films.

Keywords: average life time, CdSe QDs, microwave (MW), mass production oleic acid, Na2SeSO3

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Authors: Simon B. N. Thompson

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Retinoblastoma is a rare type of childhood genetic cancer that affects children worldwide. The diagnosis is often missed due to lack of education and difficulty in presentation of the tumor. Frequently, the tumor on the retina is noticed by photography when the red-eye flash, commonly seen in normal eyes, is not produced. Instead, a yellow or white colored patch is seen or the child has a noticeable strabismus. Early detection can be life-saving though often results in removal of the affected eye. Remaining functioning in the healthy eye when the child is young has resulted in super-vision and high or above-average intelligence. Technological advancement of cameras has helped in early detection. Brain imaging has also made possible early detection of neurological diseases and, together with the monitoring of cortisol levels and yawning frequency, promises to be the next new early diagnostic tool for the detection of neurological diseases where cortisol insufficiency is particularly salient, such as multiple sclerosis and Cushing’s disease.

Keywords: cortisol, neurological disease, retinoblastoma, Thompson cortisol hypothesis, yawning

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Authors: James Boag

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The needs of people with a diagnosis of dementia and their carers and families are physical, psychosocial, and psychological and begin at the time of diagnosis. There is frequently a lack of emotional support and counselling. Care- giving support is required from the presentation of the first symptoms of dementia until death. Alzheimer's disease begins decades before the clinical symptoms begin to appear, and in many cases, it remains undiagnosed, or diagnosed too late for any possible interventions to have any effect. However, if an incorrect diagnosis is given, it may result in a person being treated, without effect, for a type of dementia they do not have and delaying the interventions they should have received. Being diagnosed with dementia can cause emotional distress to the person, and physical and emotional support is needed, which will become more important as the disease progresses. The severity of the patient's dementia and their symptoms has a bearing of the impact on the carer and the support needed. A lack of insight and /or a denial of the diagnosis, grief, reacting to anticipated future losses, and coping methods to maximise the disease outcome, are things that should be addressed. Because of the stigma, it is important for carers not to lose contact with family and others because social isolation leads to depression and burnout. The impact on a carer's well- being and quality of life can be influenced by the severity of the illness, its type of dementia, its symptoms, healthcare support, financial and social status, career, age, health, residential setting, and relationship to the patient. Carer burnout due to lack of support leads to people diagnosed with dementia being put into residential care prematurely. Often dementia is not recognised as a terminal illness, limiting the ability of the person diagnosed with dementia and their carers to work on advance care planning and getting access to palliative and other support. Many carers have been satisfied with the physical support they were given in their everyday life, however, it was agreed that there was an immense unmet need for psychosocial support, especially after diagnosis and approaching end of life. Providing continuity and coordination of care is important. Training is necessary for providers to understand that every case is different, and they should understand the complexities. Grief, the emotional response to loss, is suffered during the progression of the disease and long afterwards, and carers should continue to be supported after the death of the person they were caring for.

Keywords: dementia, caring, challenges, needs

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Authors: Y. I. Tretyakova, S. G. Shulkina, T. Y. Kravtsova, A. A. Antipova, N. Y. Kolomeets

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The research aimed to assess the functional significance of tumor necrosis factor-alpha (TNF-α) gene polymorphism at the -308G/A (rs1800629) region and vascular endothelial growth factor A (VEGFA) gene polymorphism at the -634G/C (rs 2010963) region in the development of ulcerative colitis (UC), focusing on patients from the Perm region, Russia. We examined 70 UC patients and 50 healthy donors during the active phase of the disease. Our focus was on TNF-α and VEGF concentration in the blood serum, as well as TNF-α and VEGFA gene polymorphisms at the -308G/А and -634G/C regions, respectively. We found that TNF-α and VEGF levels were significantly higher in patients with severe UC and high endoscopic activity compared to those with milder forms of the disease and low endoscopic activity. These tests could serve as additional non-invasive markers for assessing mucosal damage in the large intestine of UC patients. The frequency of allele variations in the TNF-α gene -308G/A (rs1800629) revealed a significantly higher occurrence of the unfavorable homozygote AA in UC patients compared to donors. Additionally, the major allele G and the allele pair GG were more frequent in patients with mild to moderate disease and 1-2 degree of endoscopic activity than in those with severe UC and 3-4 degree of endoscopic activity (χ2=14.19; p=0.000). We also observed a mutant allele A and the unfavorable homozygote AA associated with severe progressive UC. The occurrence of the mutant allele increased the risk of severe UC by 5 times (OR 5.03; CI 12.07-12.21). We did not find any significant differences in the frequency of the CC homozygote (χ2=1.02; p=0.6; OR=1.32) and the mutant allele C of the VEGFA gene -634G/C (rs 2010963) (χ2=0.01; p=0.913; OR=0.97) between groups of UC patients and healthy individuals. However, we detected that the mutant allele C and the unfavorable homozygote CC of the VEGFA gene were associated with more severe endoscopic changes in the colonic mucosa of UC patients (χ2=25,76; р=0,000; OR=0,15). The presence of the mutant allele increased the risk of severe UC by 6 times (OR 6,78; CI 3,13–14,7). We found a direct correlation between TNF-α and VEGFA gene polymorphisms, increased production of the same factors, disease severity, and endoscopic activity (р=0.000). Therefore, the presence of the mutant allele A and homozygote AA of the TNF-α gene at the -308G/A region and the mutant allele C and homozygote CC of the VEGFA gene at the -634G/C region are associated with risks related to an unfavorable clinical course of UC, frequent recurrences, and rapid progression. These findings should be considered when making prognoses regarding the clinical course of the disease and selecting treatment strategies. The presence of the homozygote AA in the TNF-α gene (rs1800629) is considered a sign of genetic predisposition to UC.

Keywords: gene polymorphism, TNF-α, ulcerative colitis, VEGF

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Authors: Moushira Zaki, Wafaa Ezzat, Yasser Elhosary, Omnia Saleh

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Nonalcoholic fatty liver disease (NAFLD) has increased in conjunction with obesity. The accuracy of risk factors for detecting NAFLD in obese adolescents has not undergone a formal evaluation. The aim of this study was to evaluate predictors of NAFLD among Egyptian female obese adolescents. The study included 162 obese female adolescents. All were subjected to anthropometry, biochemical analysis and abdominal ultrasongraphic assessment. Metabolic syndrome (MS) was diagnosed according to the IDF criteria. Significant association between presence of MS and NAFLD was observed. Obese adolescents with NAFLD had significantly higher levels of ALT, triglycerides, fasting glucose, insulin, blood pressure and HOMA-IR, whereas decreased HDL-C levels as compared with obese cases without NAFLD. Receiver–operating characteristic (ROC) curve analysis shows that ALT is a sensitive predictor for NAFLD, confirming that ALT can be used as a marker of NAFLD.

Keywords: obesity, NAFLD, predictors, adolescents, Egyptians, risk factors, prevalence

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Authors: Hitoshi Minakuchi, Izumi Takei, Shu Wakino, Koichi Hayashi, Hiroshi Itoh

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Objectives: Among type 2 diabetics, patients with CKD(chronic kidney disease), insulin resistance, impaired glyconeogenesis in kidney and reduced degradation of insulin are recognized, and we observed different fluctuational patterns of blood sugar between CKD patients and non-CKD patients. On the other hand, non-dipper type blood pressure change is the risk of organ damage and mortality. We performed cross-sectional study to elucidate the characteristic of the fluctuation of blood glucose and blood pressure at insulin-treated diabetic patients with chronic kidney disease. Methods: From March 2011 to April 2013, at the Ichikawa General Hospital of Tokyo Dental College, we recruited 20 outpatients. All participants are insulin-treated type 2 diabetes with CKD. We collected serum samples, urine samples for several hormone measurements, and performed CGMS(Continuous glucose measurement system), ABPM (ambulatory blood pressure monitoring), brain computed tomography, carotid artery thickness, ankle brachial index, PWV, CVR-R, and analyzed these data statistically. Results: Among all 20 participants, hypoglycemia was decided blood glucose 70mg/dl by CGMS of 9 participants (45.0%). The event of hypoglycemia was recognized lower eGFR (29.8±6.2ml/min：41.3±8.5ml/min, P<0.05), lower HbA1c (6.44±0.57%：7.53±0.49%), higher PWV (1858±97.3cm/s：1665±109.2cm/s), higher serum glucagon (194.2±34.8pg/ml：117.0±37.1pg/ml), higher free cortisol of urine (53.8±12.8μg/day：34.8±7.1μg/day), and higher metanephrin of urine (0.162±0.031mg/day：0.076±0.029mg/day). Non-dipper type blood pressure change in ABPM was detected 8 among 9 participants with hypoglycemia (88.9%), 4 among 11 participants (36.4%) without hypoglycemia. Multiplex logistic-regression analysis revealed that the event of hypoglycemia is the independent factor of non-dipper type blood pressure change. Conclusions: Among insulin-treated type 2 diabetic patients with CKD, the events of hypoglycemia were frequently detected, and can associate with the organ derangements through the medium of non-dipper type blood pressure change.

Keywords: chronic kidney disease, hypoglycemia, non-dipper type blood pressure change, diabetic patients

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Authors: Atsuko Okazaki, Jurg Ott

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Some genetic diseases (‘digenic traits’) are due to the interaction between two DNA variants. For example, certain forms of Retinitis Pigmentosa (a genetic form of blindness) occur in the presence of two mutant variants, one in the ROM1 gene and one in the RDS gene, while the occurrence of only one of these mutant variants leads to a completely normal phenotype. Detecting such digenic traits by genetic methods is difficult. A common approach to finding disease-causing variants is to compare 100,000s of variants between individuals with a trait (cases) and those without the trait (controls). Such genome-wide association studies (GWASs) have been very successful but hinge on genetic effects of single variants, that is, there should be a difference in allele or genotype frequencies between cases and controls at a disease-causing variant. Frequent pattern mining (FPM) methods offer an avenue at detecting digenic traits even in the absence of single-variant effects. The idea is to enumerate pairs of genotypes (genotype patterns) with each of the two genotypes originating from different variants that may be located at very different genomic positions. What is needed is for genotype patterns to be significantly more common in cases than in controls. Let Y = 2 refer to cases and Y = 1 to controls, with X denoting a specific genotype pattern. We are seeking association rules, ‘X → Y’, with high confidence, P(Y = 2|X), significantly higher than the proportion of cases, P(Y = 2) in the study. Clearly, generally available FPM methods are very suitable for detecting disease-associated genotype patterns. We use fpgrowth as the basic FPM algorithm and built a framework around it to enumerate high-frequency digenic genotype patterns and to evaluate their statistical significance by permutation analysis. Application to a published dataset on opioid dependence furnished results that could not be found with classical GWAS methodology. There were 143 cases and 153 healthy controls, each genotyped for 82 variants in eight genes of the opioid system. The aim was to find out whether any of these variants were disease-associated. The single-variant analysis did not lead to significant results. Application of our FPM implementation resulted in one significant (p < 0.01) genotype pattern with both genotypes in the pattern being heterozygous and originating from two variants on different chromosomes. This pattern occurred in 14 cases and none of the controls. Thus, the pattern seems quite specific to this form of substance abuse and is also rather predictive of disease. An algorithm called Multifactor Dimension Reduction (MDR) was developed some 20 years ago and has been in use in human genetics ever since. This and our algorithms share some similar properties, but they are also very different in other respects. The main difference seems to be that our algorithm focuses on patterns of genotypes while the main object of inference in MDR is the 3 × 3 table of genotypes at two variants.

Keywords: digenic traits, DNA variants, epistasis, statistical genetics

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Authors: Shinen B., Bavor J., Dorjkhand B., Suvd B., Maitsetseg B.

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A number of remediation techniques are available for the treatment of soils and sediments contaminated by heavy metals. However, some of these techniques are expensive and environmentally disruptive. Nanomaterials are used in the environment as environmental catalysts to convert toxic substances from water, soil, and sediment into environmentally benign compounds. This study was carried out to scrutinize the feasibility of vivianite nanoparticles for remediation of soils contaminated with heavy metals. Column experiments were performed in the laboratory to examine nanoparticle sequestration of metal in soil amended with vivianite nanoparticle suspension. The effect of environmental parameters such as temperature, pH and redox potential on metal leachability and bioavailability of soil amended with nanoparticle suspension was examined and compared with non-amended soils. The vivianite was effective in reducing the leachability of metals in soils. It is suggested that vivianite nanoparticles could be applied for the remediation of contaminated sites polluted by heavy metals due to mining activities, particularly in Mongolia, where mining industries have been developing rapidly in the last decade.

Keywords: bioavailability, heavy metals, nanoparticles, remediation

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Authors: Chawarat Rotejanaprasert, Andrew Lawson

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Early detection of unusual health events depends on the ability to detect rapidly any substantial changes in disease, thus facilitating timely public health interventions. To assist public health practitioners to make decisions, statistical methods are adopted to assess unusual events in real time. We introduce a surveillance Kullback-Leibler (SKL) measure for timely detection of disease outbreaks for small area health data. The detection methods are compared with the surveillance conditional predictive ordinate (SCPO) within the framework of Bayesian hierarchical Poisson modeling and applied to a case study of a group of respiratory system diseases observed weekly in South Carolina counties. Properties of the proposed surveillance techniques including timeliness and detection precision are investigated using a simulation study.

Keywords: Bayesian, spatial, temporal, surveillance, prospective

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Authors: Olofintoye Lawrence Kayode, Olorunniyi Omojola Felix

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Schistosomiasis is a vector-borne water-based disease transmitted by Bulinus globosus, causing haematuria in the urine of man, while fascioliasis is a trematode zoonosis infectious transmitted by Lymnaea natalensis causing liver disease in man and animals. Adult Bulinus globosus and Lymnaea natalensis were used for the experiment. Aqueous leaf extract of Ageratum conyzoides and Datura stramonium were prepared into 25, 50, 75, 100, 200 and 400 ppm concentrations. Ten snails of each species were exposed to different concentrations in triplicates, and dechlorinated water was used as control at 24h, 48h, and 72h exposure. The results revealed that 100 ppm of both plants leaves extracts indicated mortality rates between 76.7% and 100% at 24h, 48h, and 72h for both snail species. (P<0.05). In conclusion, the extract exercised molluscicidal activity to control the snail vector at lethal doses LC₅₀ (66.611- 72.021 ppm), CI = 63.083-77.90ppm and LC₉₀ (92.623-102.350), CI = 87.715 -110.12 ppm.

Keywords: snail, plant leaf, aqueous extract, mortality

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Authors: Tsu-Yun Chiu, Tsung-Hsueh Lu, Tain-Junn Cheng

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Background: Traditional chronic disease management did not pay attention to effects of geographic factors on the compliance of treatment regime, which resulted in geographic inequality in outcomes of chronic disease management. This study aims to examine the geographic distribution and clustering of quality indicators of diabetes care. Method: We first extracted address, demographic information and quality of care indicators (number of visits, complications, prescription and laboratory records) of patients with diabetes for 2014 from medical information system in a medical center in Tainan City, Taiwan, and the patients’ addresses were transformed into district- and village-level data. We then compared the differences of geographic distribution and clustering of quality of care indicators between districts and villages. Despite the descriptive results, rate ratios and 95% confidence intervals (CI) were estimated for indices of care in order to compare the quality of diabetes care among different areas. Results: A total of 23,588 patients with diabetes were extracted from the hospital data system; whereas 12,716 patients’ information and medical records were included to the following analysis. More than half of the subjects in this study were male and between 60-79 years old. Furthermore, the quality of diabetes care did indeed vary by geographical levels. Thru the smaller level, we could point out clustered areas more specifically. Fuguo Village (of Yongkang District) and Zhiyi Village (of Sinhua District) were found to be “hotspots” for nephropathy and cerebrovascular disease; while Wangliau Village and Erwang Village (of Yongkang District) would be “coldspots” for lowest proportion of ≥80% compliance to blood lipids examination. On the other hand, Yuping Village (in Anping District) was the area with the lowest proportion of ≥80% compliance to all laboratory examination. Conclusion: In spite of examining the geographic distribution, calculating rate ratios and their 95% CI could also be a useful and consistent method to test the association. This information is useful for health planners, diabetes case managers and other affiliate practitioners to organize care resources to the areas most needed.

Keywords: catchment area of healthcare, chronic disease management, Geographic information system, quality of diabetes care

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Authors: Frida Carrillo Morales, Maria Maricela Carrasco Yépez, Saúl Rojas Hernández

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Naegleria fowleri is the causative agent of primary amebic meningoencephalitis, this disease is acute and fulminant that affects humans. It has been reported that despite the existence of therapeutic options against this disease, its mortality rate is 97%. Therefore, the need arises to have vaccines that confer protection against this disease and, in addition to developing adjuvants to enhance the immune response. In this regard, in our work group, we obtained a peptide designed from the membrane protein MP2CL5 of Naegleria fowleri called Smp145 that was shown to be immunogenic; however, it would be of great importance to enhance its immunological response, being able to co-administer it with a non-toxic adjuvant. Therefore, the objective of this work was to carry out the bioinformatic design of a peptide of the Naegleria fowleri membrane protein MP2CL5 conjugated with a non-toxic modified adjuvant from the native A1 structure of Cholera Toxin. For which different bioinformatics tools were used to obtain a model with a modification in amino acid 61 of the A1 subunit of the CT (CTA1), to which the Smp145 peptide was added and both molecules were joined with a 13-glycine linker. As for the results obtained, the modification in CTA1 bound to the peptide produces a reduction in the toxicity of the molecule in in silico experiments, likewise, the prediction in the binding of Smp145 to the receptor of B cells suggests that the molecule is directed in specifically to the BCR receptor, decreasing its native enzymatic activity. The stereochemical evaluation showed that the generated model has a high number of adequately predicted residues. In the ERRAT test, the confidence with which it is possible to reject regions that exceed the error values was evaluated, in the generated model, a high score was obtained, which determines that the model has a good structural resolution. Therefore, the design of the conjugated peptide in this work will allow us to proceed with its chemical synthesis and subsequently be able to use it in the mouse meningitis protection model caused by N. fowleri.

Keywords: immunology, vaccines, pathogens, infectious disease

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Authors: Abdullah A. Al Qurashi, Hattan A. Hassani, Bader K. Alaslap

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Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) is an uncommon, inheritable cardiac disorder characterized by the progressive substitution of cardiac myocytes by fibro-fatty tissues. This pathologic substitution predisposes patients to ventricular arrhythmias and right ventricular failure. The underlying genetic defect predominantly involves genes encoding for desmosome proteins, particularly plakophilin-2 (PKP2). These aberrations lead to impaired cell adhesion, heightening the susceptibility to fibrofatty scarring under conditions of mechanical stress. Primarily, ARVD/C affects the right ventricle, but it can also compromise the left ventricle, potentially leading to biventricular heart failure. Clinical presentations can vary, spanning from asymptomatic individuals to those experiencing palpitations, syncopal episodes, and, in severe instances, sudden cardiac death. The establishment of a diagnostic criterion specifically tailored for ARVD/C significantly aids in its accurate diagnosis. Nevertheless, the task of early diagnosis is complicated by the disease's frequently asymptomatic initial stages, and the overall rarity of ARVD/C cases reported globally. In some cases, as exemplified by the adult female patient in this report, the disease may advance to terminal stages, rendering therapies like Ventricular Tachycardia (VT) ablation ineffective. This case underlines the necessity for increased awareness and understanding of ARVD/C to aid in its early detection and management. Through such efforts, we aim to decrease morbidity and mortality associated with this challenging cardiac disorder.

Keywords: arrhythmogenic right ventricular dysplasia, cardiac disease, interventional cardiology, cardiac electrophysiology

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Authors: Vivek Rangarajan, Kim G. Klarke

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With overpopulation threatening the world’s ability to feed itself, food production and protection has become a major issue, especially in developing countries. Almost one-third of the food produced for human consumption, around 1.3 billion tonnes, is either wasted or lost annually. Postharvest decay in particular constitutes a major cause of crop loss with about 20% of fruits and vegetables produced lost during postharvest storage, mainly due to fungal disease. Some of the major phytopathogenic fungi affecting postharvest fruit crops in South Africa include Aspergillus, Botrytis, Penicillium, Alternaria and Sclerotinia spp. To date control of fungal phytopathogens has primarily been dependent on synthetic chemical fungicides, but these chemicals pose a significant threat to the environment, mainly due to their xenobiotic properties and tendency to generate resistance in the phytopathogens. Here, an environmentally benign alternative approach to control postharvest fungal phytopathogens in perishable fruit crops has been presented, namely the application of a bio-fungicide in the form of lipopeptide molecules. Lipopeptides are biosurfactants produced by Bacillus spp. which have been established as green, nontoxic and biodegradable molecules with antimicrobial properties. However, since the Bacillus are capable of producing a large number of lipopeptide homologues with differing efficacies against distinct target organisms, the lipopeptide production conditions and strategy are critical to produce the maximum lipopeptide concentration with homologue ratios to specification for optimum bio-fungicide efficacy. Process conditions, and their impact on Bacillus lipopeptide production, were evaluated in fully instrumented laboratory scale bioreactors under well-regulated controlled and defined environments. Factors such as the oxygen availability and trace element and nitrate concentrations had profound influences on lipopeptide yield, productivity and selectivity. Lipopeptide yield and homologue selectivity were enhanced in cultures where the oxygen in the sparge gas was increased from 21 to 30 mole%. The addition of trace elements, particularly Fe2+, increased the total concentration of lipopeptides and a nitrate concentration equivalent to 8 g/L ammonium nitrate resulted in optimum lipopeptide yield and homologue selectivity. Efficacy studies of the culture supernatant containing the crude lipopeptide mixture were conducted using phytopathogens isolated from fruit in the field, identified using genetic sequencing. The supernatant exhibited antifungal activity against all the test-isolates, namely Lewia, Botrytis, Penicillium, Alternaria and Sclerotinia spp., even in this crude form. Thus the lipopeptide product efficacy has been confirmed to control the main diseases, even in the basic crude form. Future studies will be directed towards purification of the lipopeptide product and enhancement of efficacy.

Keywords: antifungal efficacy, biocontrol, lipopeptide production, perishable crops

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Authors: Federico Herrera, Valle Gomez García de Soria, Itxaso Portero Sainz, Carlos Fernández Arandojo, Mercedes Royg, Ana Marcos Jimenez, Anna Kreutzman, Cecilia MuñozCalleja

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Introduction: Graft-versus-host disease (GVHD) still remains the major complication associated with allogeneic stem cell transplantation (SCT). The pathogenesis involves migration of donor naïve T-cells into recipient secondary lymphoid organs. Two molecules are important in this process: CD62L and CCR7, which are characteristically expressed in naïve/central memory T-cells. With this background, we aimed to study the influence of CCR7 and CD62L on donor lymphocytes in the development and severity of GVHD. Material and methods: This single center study included 98 donor-recipient pairs. Samples were collected prospectively from the apheresis product and phenotyped by flow cytometry. CCR7 and CD62L expression in CD4+ and CD8+ T-cells were compared between patients who developed acute (n=40) or chronic GVHD (n=33) and those who did not (n=38). Results: The patients who developed acute GVHD were transplanted with a higher percentage of CCR7+CD4+ T-cells (p = 0.05) compared to the no GVHD group. These results were confirmed when these patients were divided in degrees according to the severity of the disease; the more severe disease, the higher percentage of CCR7+CD4+ T-cells. Conversely, chronic GVHD patients received a higher percentage of CCR7+CD8+ T-cells (p=0.02) in comparison to those who did not develop the complication. These data were also confirmed when patients were subdivided in degrees of the disease severity. A multivariable analysis confirmed that percentage of CCR7+CD4+ T-cells is a predictive factor of acute GVHD whereas the percentage of CCR7+CD8+ T-cells is a predictive factor of chronic GVHD. In vitro functional assays (migration and activation assays) supported the idea of CCR7+ T-cells were involved in the development of GVHD. As low levels of CD62L expression were detected in all apheresis products, we tested the hypothesis that CD62L was shed during apheresis procedure. Comparing CD62L surface levels in T-cells from the same donor immediately before collecting the apheresis product, and the final apheresis product we found that this process down-regulated CD62L in both CD4+ and CD8+ T cells (p=0.008). Interestingly, when CD62L levels were analysed in days 30 or 60 after engraftment, they recovered to baseline (p=0.008). However, to investigate the relation between CD62L expression and the development of GVHD in the recipient samples after the engraftment, no differences were observed comparing patients with GVHD to those who did not develop the disease. Discussion: Our prospective study indicates that the CCR7+ T-cells from the donor, which include naïve and central memory T-cells, contain the alloreactive cells with a high ability to mediate GVHD (in the case of both migration and activation). Therefore we suggest that the proportion and functional properties of CCR7+CD4+ and CCR7+CD8+ T-cells in the apheresis could act as a predictive biomarker to both acute and chronic GVHD respectively. Importantly, our study precludes that CD62L is lost in the apheresis and therefore it is not a reliable biomarker for the development of GVHD.

Keywords: CCR7, CD62L, GVHD, SCT

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Authors: Nandhakumar Elumalai, Purushothaman Ayyakannu, Sachidanandam T. Panchanatham

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Background: Understanding the basic mechanisms and factors underlying the tumor growth and invasion has gained attention in recent times. The processes of angiogenesis and apoptosis are known to play a vital role in various stages of cancer. The vascular endothelial growth factor (VEGF) is well established as one of the key regulators of tumor angiogenesis while MMPs are known for their exclusive ability to degrade ECM. Objective: The present study was designed to evaluate the pro apoptotic and anti angiogenic activity of the herbal formulation Shemamruthaa. The anticancer activity of Shemamruthaa was tested in breast cancer cell line (MCF-7). Results of MTT, trypan blue and flow cytometric analysis of apoptotis suggested that Shemamruthaa can induce cytotoxicity in cancer cells, in a concentration- and time dependent manner and induce apoptosis. With these results, we further evaluated the antiangiogenic and pro-apoptotic activities of Shemamruthaa in DMBA induced mammary carcinoma in Sprague Dawley rats. Flavono tumour was induced in 8-week-old Sprague-Dawley rats by gastric intubation of 25 mg DMBA in 1ml olive oil. After 90 days of induction period, the rats were orally administered with Shemamruthaa (400 mg/kg body wt) for 45 days. Treatment with the drug SM significantly modulated the expression of p53, MMP-2, MMP-3, MMP-9 and VEGF by means of its anti angiogenic and protease inhibiting activity. Conclusion: Based on these results, it might be concluded that the formulation, Shemamruthaa, constituted of dried flowers of Hibiscus rosa-sinensis, fruits of Emblica officinalis, and honey has been found to exhibit pronounced antiproliferative and apoptotic effects. This enhanced anticancer effect of Shemamruthaa might be attributed to the synergistic action of polyphenols such as flavonoids, tannins, alkaloids, glycosides, saponins, steroids, terpenoids, vitamin C, niacin, pyrogallol, hydroxymethylfurfural, trilinolein, and other compounds present in the formulation. Collectively, these results demonstrate that Shemamruthaa holds potential to be developed as a potent chemotherapeutic agent against mammary carcinoma.

Keywords: Shemamruthaa, flavonoids, MCF-7 cell line, mammary cancer

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Authors: Yasir Karabacak

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Objective: The aim of periodontal therapy is to control and eliminate inflammation in order halt disease progression. The initial periodontal therapy (IPT) including scaling and root planing (SRP) can control periodontal disease in most cases of periodontitis; also maintaining good oral hygiene by the patient is fundamental. The aim of this case report is to present IPT and to present 3-month follow-up results in a patient with periodontitis. Materials and Methods IPT of a 63-year-old non-smoker male with generalized periodontitis is presented. The patient had no history of systemic disease. The intraoral examination reveals marked gingival inflammation as well as plaque accumulation and significant calculus deposits. On radiographic examination, severe bone loss was evident. The patient was diagnosed with generalized advanced periodontitis. Initial periodontal therapy including oral hygiene instructions and quadrant-based SRP under local anesthesia was performed using hand and ultrasonic instruments. No antibiotics were prescribed. The patient was recalled 4 weeks after IPT. Results Favorable clinical improvement was obtained. Gingival inflammation was resolved significantly. A reduction of the mean probing depth from 2.4 mm at baseline to 1.9 mm was observed. The patient presented with a good standard of oral hygiene. The plaque scores decreased from 54.0% at baseline to 17.0%. In addition, the percentage of sites with bleeding on probing decreased from 80.0% at baseline to 44.0%. The patient was scheduled for maintenance therapy every three months. Conclusion: The level of oral hygiene has a great impact on periodontal treatment outcome and supports periodontal therapy properly.

Keywords: initial periodontal, therapy and follow-up in a periodontitis, patient, a case report

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Authors: Mehdi Razeghi

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Background: The purpose of this case series was to quantify gait to study muscular dystrophy disease. In this research, the quantitative differences between normal and waddling gaits were assessed by force plate analysis. Methods: Nineteen myopathy patients and twenty normal subjects serving as the control group participated in this research. In this study, quantitative analyses of gait have been used to investigate the differences between the mobility of normal subjects and myopathy patients. This study was carried out at the Iranian Muscular Dystrophy Association in Boali Hospital, Tehran, Iran, from October 2015 to July 2020. Patient data were collected from Iranian Muscular Dystrophy Association members. individuals signed an informed consent form approved by the ethics committee of the Azad University. All of the gait tests were performed using a Kistler force platform. Participants walked at a self-selected speed, barefoot, independently, and without assistive devices. Results: Our findings indicate that there were no significant differences between the patients and the control group in the anterior-posterior components of the ground reaction forces; however, there were considerable differences in the force components between the groups in the medial-lateral and vertical directions of the ground reaction force. In addition, there were significant differences in the time parameters between the groups in the vertical and medial-lateral directions.

Keywords: biomechanics, force plate analysis, gait disorder, ground reaction force, kinetic analysis, myopathy disease, rehabilitation engineering

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Authors: Gilbert Makanda

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The problem of the teaching of mathematics is studied using differential equations. A mathematical model for knowledge acquisition in mathematics is developed. In this study we adopt the mathematical model that is normally used for disease modelling in the teaching of mathematics. It is assumed that teaching is 'infecting' students with knowledge thereby spreading this knowledge to the students. It is also assumed that students who gain this knowledge spread it to other students making disease model appropriate to adopt for this problem. The results of this study show that increasing recruitment rates, learning contact with teachers and learning materials improves the number of knowledgeable students. High dropout rates and forgetting taught concepts also negatively affect the number of knowledgeable students. The developed model is then solved using Matlab ODE45 and \verb"lsqnonlin" to estimate parameters for the actual data.

Keywords: differential equations, knowledge acquisition, least squares, dynamical systems

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Authors: Hyunho Shin, Jaekwang Jung, Jeongho Park, Sungwon Hwang

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For the application of graphene quantum dots (GQDs) to optoelectronic nanodevices, it is of critical importance to understand the mechanisms which result in novel phenomena of their light absorption/emission. The optical transitions are known to be available up to ~6 eV in GQDs, especially useful for ultraviolet (UV) photodetectors (PDs). Here, we present size-dependent shape/edge-state variations of GQDs and visible photoluminescence (PL) showing anomalous size dependencies. With varying the average size (da) of GQDs from 5 to 35 nm, the peak energy of the absorption spectra monotonically decreases, while that of the visible PL spectra unusually shows nonmonotonic behaviors having a minimum at diameter ∼17 nm. The PL behaviors can be attributed to the novel feature of GQDs, that is, the circular-to-polygonal-shape and corresponding edge-state variations of GQDs at diameter ∼17 nm as the GQD size increases, as demonstrated by high resolution transmission electron microscopy. We believe that such a comprehensive scheme in designing device architecture and the structural formulation of GQDs provides a device for practical realization of environmentally benign, high performance flexible devices in the future.

Keywords: graphene, quantum dot, size, photoluminescence

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Authors: Ognen Kostovski, Svetozar Antovic, Rubens Jovanovic, Irena Kostovska, Nikola Jankulovski

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Introduction:Colorectal carcinoma (CRC) is one of the most common malignancies in the world. The cancer stem cell (CSC) markers are associated with aggressive cancer types and poor prognosis. The aim of study was to determine whether the expression of colorectal cancer stem cell markers CD133 and CD44 could be significant in prediction of clinically aggressive form of CRC. Materials and methods: Our study included ninety patients (n=90) with CRC. Patients were divided into two subgroups: with metatstatic CRC and non-metastatic CRC. Tumor samples were analyzed with standard histopathological methods, than was performed immunohistochemical analysis with monoclonal antibodies against CD133 and CD44 stem cell markers. Results: High coexpression of CD133 and CD44 was observed in 71.4% of patients with metastatic disease, compared to 37.9% in patients without metastases. Discordant expression of both markers was found in 8% of the subgroup with metastatic CRC, and in 13.4% of the subgroup without metastatic CRC. Statistical analyses showed a significant association of increased expression of CD133 and CD44 with the disease stage, T - category and N - nodal status. With multiple regression analysis the stage of disease was designate as a factor with the greatest statistically significant influence on expression of CD133 (p <0.0001) and CD44 (p <0.0001). Conclusion: Our results suggest that the coexpression of CD133 and CD44 have an important role in prediction of clinically aggressive form of CRC. Both stem cell markers can be routinely implemented in standard pathohistological diagnostics and can be useful markers for pre-therapeutic oncology screening.

Keywords: colorectal carcinoma, stem cells, CD133+, CD44+

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Authors: Perumalsamy Muthiah, Murugesan Thanapalan

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The remains of cheese production contain nutritional value added proteins viz., α-Lactalbumin, β-Lactoglobulin representing 80- 90% of the total volume of milk entering the process. Although several possibilities for cheese-whey exploitation have been assayed, approximately half of world cheese-whey production is not treated but is discarded as effluent. It is necessary to develop an effective and environmentally benign extraction process for the recovery of value added cheese whey proteins. Recently aqueous two phase system (ATPS) have emerged as potential separation process, particularly in the field of biotechnology due to the mild conditions of the process, short processing time, and ease of scale-up. In order to design an ATPS process for the recovery of cheese whey proteins, development of phase diagram and the effect of system parameters such as pH, types and the concentrations of the phase forming components, temperature, etc., on the partitioning of proteins were addressed in order to maximize the recovery of proteins. Some of the practical problems encountered in the application of aqueous two-phase systems for the recovery of Cheese whey proteins were also discussed.

Keywords: aqueous two-phase system, phase diagram, extraction, cheese whey

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Authors: Jitaree Tantiyasawatdikul, Bantita Jadnok, Sarunya Tijana

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Background: Nutritional status is an important factor before, during, and after an operation. It can help wound healing. If the patients have good nutritional status before and after an operation, wound healing can occur more easily. It can strengthen the immune system leading to decreased infection, reduced length of stay, and reducing the cost to patients and caregivers. Therefore, screening to evaluate the nutritional status of patients in 3B becomes the database for further developing the treatment and also will lead to excellent service from the interdisciplinary team. Objective: To study the nutritional status of patients in surgical ward 3B at Surgical and Orthopedics Nursing Division, Srinagarind Hospital. Method: A descriptive study, to evaluate the nutritional status of 86 patients admitted in 3B between October 2014 and March 2015.The instruments used in this study consisted of two parts: 1) personal data, 2) Screening nutritional status. The data were analyzed by percentage and mean. Results: A sample population of 86 patients aged 22-81 years old, mean age 52.59years, 90.69% are married, female were 55.81%, regular diet 70.93%, patients with no problem oral cavity was 87.21%.The sample population had high incidence of CA 47.67% and secondly cardiovascular disease 36.05 %. Patients with high-risk nutrition was 12.79 % including 45.45% cardiovascular disease and 36.36% CA. Screening of nutritional status of high-risk nutrition was 39.36% severe triceps skinfold (TSF), severe mid-arm muscle circumference(MAMC) 9.09% and severe total lymphocyte 39.36%. Conclusion: The result of nutritional status screening of surgical ward 3B found 12.79% patients with high-risk nutrition including 45.45% with cardiovascular disease .There was no problem with oral cavity and eating.

Keywords: nutritional status, screening, surgical patients, 3B ward, Srinagarind Hospital

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