Search results for: blood cancer
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4433

Search results for: blood cancer

2903 Retinal Vascular Tortuosity in Obstructive Sleep Apnea-COPD Overlap Patients

Authors: Rabab A. El Wahsh, Hatem M. Marey, Maha Yousif, Asmaa M. Ibrahim

Abstract:

Background: OSA and COPD are associated with microvascular changes. Retinal microvasculature can be directly and non-invasively examined. Aim: to evaluate retinal vascular tortuosity in patients with COPD, OSA, and overlap syndrome. Subjects and method: Sixty subjects were included; 15 OSA patients, 15 COPD patients, 15 COPD-OSA overlap patients, and 15 matched controls. They underwent digital retinal photography, polysomnography, arterial blood gases, spirometry, ESS, and stop-bang questionnaires. Results: Tortuosity of most retinal vessels was higher in all patient groups compared to the control group; tortuosity was more marked in overlap syndrome. There was a negative correlation between tortuosity of retinal vessels and PO2, O2 saturation, and minimum O2 desaturation, and a positive correlation with PCO2, AHI, O2 desaturation index, BMI and smoking index. Conclusion: Retinal vascular tortuosity occurs in OSA, COPD and overlap syndrome. Retinal vascular tortuosity is correlated with arterial blood gases parameters, polysomnographic findings, smoking index and BMI.

Keywords: OSA, COPD, overlap syndrome, retinal vascular tortuosity

Procedia PDF Downloads 79
2902 Validation of an Educative Manual for Patients with Breast Cancer Submitted to Radiation Therapy

Authors: Flavia Oliveira de A. M. Cruz, Edison Tostes Faria, Paula Elaine D. Reis

Abstract:

When the breast is submitted to radiation therapy (RT), the most common effects are pain, skin changes, mobility restrictions, local sensory alteration, and fatigue. These effects, if not managed properly, may reduce the quality of life of cancer patients and may lead to the treatment discontinuation. Therefore, promoting knowledge and guidelines for symptom management remain a high priority for patients and a challenge for health professionals, due to the need to handle side effects in a population with a life-threatening disease. Printed materials are important strategies for supporting educative activities since they help the individual to assimilate and understand the amount of information transmitted. Nurses' behavior can be systematized through the use of an educative manual, which may be effective in promoting information regarding the treatment, self-care and how to control the effects of RT at home. In view of the importance of guaranteeing the validity of the material before its use, the objective of this research was to validate the content and appearance of an educative manual for breast cancer patients undergoing RT. The Theory of Psychometrics was used for the validation process in this descriptive methodological research. A minimum agreement rate (AR) of 80% was considered to guarantee the validity of the material. The data were collected from October to December 2017, by means of two assessments tools, constructed in the form of a Likert scale, with five levels of understanding. These instruments addressed different aspects of the evaluation, in view of two different groups of participants; 17 experts in the theme area of the educative manual, and 12 women that received RT previously to treat breast cancer. The manual was titled 'Orientation Manual: radiation therapy in breast', and was focused on breast cancer patients attended at the Department of Oncology of the Brasília University Hospital (UNACON/HUB). The research project was submitted to the Research Ethics Committee at the School of Health Sciences of the University of Brasília (CAAE: 24592213.1.0000.0030). Only two items of the assessment tool for the experts, one related to the manual's ability to promote behavioral and attitude changes and the other related to the extent of its use for other health services, obtained AR < 80% and were reformulated based on the participants' suggestions and in the literature. All other items were considered appropriate and/or complete appropriate in the three blocks proposed for the experts: objectives - 89%, structure and form - 93%, and relevance - 93%; and good and/or very good in the five blocks of analysis proposed for patients: objectives - 100%, organization - 100%, writing style - 100%, appearance - 100%, and motivation. The appearance and content validation of the educative manual proposed were attended to. The educative manual was considered relevant and pertinent and may contribute to the understanding of the therapeutic process by breast cancer patients during RT, as well as support clinical practice through the nursing consultation.

Keywords: oncology nursing, nursing care, validation studies, educational technology

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2901 Impact of Breed and Physiological Status on Blood Content of Goats in Arid Conditions of Algeria

Authors: Lilia Belkacem, Zahra Rouabah, Assia Allaoui, Karina Bachtarzi, Souhila Belkadi, Boubakeur Safsaf, Madjid Tlidjane

Abstract:

The Damascus breed, known for its prolificacy and milking ability, is recently imported in Algeria. Farmers tend to improve the local native herds by crossbreeding with Damascus bucks. The aim of the current investigation was to study the effects of physiological status on blood progesterone and some biochemical parameters in Shami goats and their crosses with local breed in arid conditions of Algeria. Ten does with an age range of 1.5- 3 years and BSC between 2.5 and 3.5 were used. Female goats were divided into two groups of five animals each: Damascus, and crossbred (Damascus x Arbia). All females were estrus synchronized and naturally mated. Blood samples were collected before intravaginal sponge insertion (non- pregnant), in early (30 days after sponge removal), mid (90 days), late pregnancy (130 days) and after kidding (30 days post-partum). Results demonstrate a significant effect of the reproductive stage on progesterone (P4) levels in both groups, on glycemia and cholesterolemia in crossbred does (p<0.05) and on albuminemia and uremia in Damascus ones. Concentrations of triglycerides, total proteins, globulin and creatinine revealed no significant difference between physiological phases in both groups (p>0.05). Breed effect was detected in early and mid-pregnancy for P4, in early pregnancy and lactation for total proteins and in lactation for globulin with lower concentrations in Damascus compared to crossbred does. Changes in P4 and biochemical profiles of both groups reflect the female goat’s adaptation to increased requirement of gestation and lactation in arid conditions of Algeria.

Keywords: damascus goat, crossbred, reproductive status, progesterone, biochemical metabolites

Procedia PDF Downloads 65
2900 Why is the Recurrence Rate of Residual or Recurrent Disease Following Endoscopic Mucosal Resection (EMR) of the Oesophageal Dysplasia’s and T1 Tumours Higher in the Greater Midlands Cancer Network?

Authors: Harshadkumar Rajgor, Jeff Butterworth

Abstract:

Background: Barretts oesophagus increases the risk of developing oesophageal adenocarcinoma. Over the last 40 years, there has been a 6 fold increase in the incidence of oesophageal adenocarcinoma in the western world and the incidence rates are increasing at a greater rate than cancers of the colon, breast and lung. Endoscopic mucosal resection (EMR) is a relatively new technique being used by 2 centres in the greater midlands cancer network. EMR can be used for curative or staging purposes, for high-grade dysplasia’s and T1 tumours of the oesophagus. EMR is also suitable for those who are deemed high risk for oesophagectomy. EMR has a recurrence rate of 21% according to the Wiesbaden data. Method: A retrospective study of prospectively collected data was carried out involving 24 patients who had EMR for curative or staging purposes. Complications of residual or recurrent disease following EMR that required further treatment were investigated. Results: In 54% of cases residual or recurrent disease was suspected. 96% of patients were given clear and concise information regarding their diagnosis of high-grade dysplasia or T1 tumours. All 24 patients consulted the same specialist healthcare team. Conclusion: EMR is a safe and effective treatment for patients who have high-grade dysplasia and T1NO tumours. In 54% of cases residual or recurrent disease was suspected. Initially, only single resections were undertaken. Multiple resections are now being carried out to reduce the risk of recurrence. Complications from EMR remain low in this series and consisted of a single episode of post procedural bleeding.

Keywords: endoscopic mucosal resection, oesophageal dysplasia, T1 tumours, cancer network

Procedia PDF Downloads 322
2899 Awareness Creation of Benefits of Antitrypsin-Free Nutraceutical Biopowder for Increasing Human Serum Albumin Synthesis as Possible Adjunct for Management of MDRTB or MDRTB-HIV Patients

Authors: Vincent Oghenekevbe Olughor, Olusoji Mayowa Ige

Abstract:

Except for a preexisting liver disease and malnutrition, there are no predilections for low serum albumin (SA) levels in humans. At normal reference levels (4.0-6.0g/dl) SA is a universal marker for mortality and morbidity risks assessments where depletion by 1.0g/dl increases mortality risk by 137% and morbidity by 89%.It has 40 known functions contributing significantly to the sustenance of human life. A depletion in SA to <2.2g/dl, in most clinical settings worldwide, leads to loss of oncotic pressure of blood causing clinical manifestations of bipedal Oedema, in which the patients remain conscious. SA also contributes significantly to buffering of blood to a life-sustaining pH of 7.35-7.45. A drop in blood pH to <6.9 will lead to instant coma and death, which can occur after SA continues to deplete after manifestations of bipedal Oedema. In an intervention study conducted in 2014 following the discovery that “SA is depleted during malaria fever”, a Nutraceutical formulated for use as treatment adjunct to prevent SA depletions during malaria to <2.4g/dl after Efficacy testing was found to be satisfactory. There are five known types of Malaria caused by Apicomplexan parasites, Plasmodium: the most lethal being that caused by Plasmodium falciparum causing malignant tertian malaria, in which the fever was occurring every 48 hours coincides with the dumping of malaria-toxins (Hemozoin) into blood, causing contamination: blood must remain sterile. Other Apicomplexan parasites, Toxoplasma and Cryptosporidium, are opportunistic infections of HIV. Separate studies showed SA depletions in MDRTB (multidrug resistant TB), and MDRTB-HIV patients by the same mechanism discovered with malaria and such depletions will be further complicated whenever Apicomplexan parasitic infections co-exist. Both Apicomplexan parasites and the TB parasite belong to the Obligate-group of Parasites, which are parasites that replicate only inside its host; and most of them have capacities to over-consume host nutrients during parasitaemia. In MDRTB patients the body attempts repeatedly to prevent depletions in SA to critical levels in the presence of adequate nutrients and only for a while in MDRTB-HIV patients. These groups of patients will, therefore, benefit from the already tested Nutraceutical in malaria patients. The Nutraceutical bio-Powder was formulated (to BP 1988 specification) from twelve nature-based food-grade nutrients containing all dedicated nutrients for ensuring improved synthesis of Albumin by the liver. The Nutraceutical was administered daily for 38±2days in 23 children, in a prospective phase-2 clinical trial, and its impact on body weight and core blood parameters were documented at the start and end of efficacy testing period. Sixteen children who did not experience malaria-induced depletions of SA had significant SA increase; seven children who experienced malaria-induced depletions of SA had insignificant SA decrease. The Packed Cell Volume Percentage (PCV %), a measure of the Oxygen carrying capacity of blood and the amount of nutrients the body can absorb, increased in both groups. The total serum proteins (SA+ Globulins) increased or decreased within the continuum of normal. In conclusion, MDRTB and MDRTB-HIV patients will benefit from a variant of this Nutraceutical when used as treatment adjunct.

Keywords: antitrypsin-free Nutraceutical, apicomplexan parasites, no predilections for low serum albumin, toxoplasmosis

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2898 Pharmacokinetic and Tissue Distribution of Etoposide Loaded Modified Glycol Chitosan Nanoparticles

Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Mehboob Alam

Abstract:

The development of efficient delivery systems remains a major concern in cancer chemotherapy as many efficacious anticancer drugs are hydrophobic and difficult to formulate. Nanomedicines based on drug-loaded amphiphilic glycol chitosan micelles offer potential advantages for the formulation of drugs such as etoposide that may improve the pharmacokinetics and reduce the formulation-related adverse effects observed with current formulations. Amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxysuccinimide and quaternization to glycol chitosan backbone. To this end, a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternization, yielding a 13 kDa amphiphilic polymer. Micelles prepared from this amphiphilic polymer had a size of 162nm and were able to encapsulate up to 3 mg/ml etoposide. Pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drugs after intravenous administration. AUC 0.5-24h showed statistically significant difference in ETP-GCPQ vs. Commercial preparation in liver (25 vs.70, p<0.001), spleen (27 vs.36, p<0.05), lungs (42 vs.136,p<0.001),kidneys(25 vs.70,p< 0.05),and brain(19 vs.9,p<0.001). ETP-GCPQ crossed the blood-brain barrier, and 4, 3.5, 2.6, 1.8, 1.7, 1.5, and 2.5 fold higher levels of etoposide were observed at 0.5, 1, 2, 4, 6, 12, and 24hrs; respectively suggesting these systems could deliver hydrophobic anticancer drugs such as etoposide to tumors but also increased their transport through the biological barriers, thus making it a good delivery system

Keywords: glycol chitosan, micelles, pharmacokinetics, tissue distribution

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2897 Foslip Loaded and CEA-Affimer Functionalised Silica Nanoparticles for Fluorescent Imaging of Colorectal Cancer Cells

Authors: Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, Thomas Hughes, Paul Millner, David G. Jayne

Abstract:

Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.

Keywords: colorectal cancer, silica nanoparticles, Affimers, antibodies, imaging

Procedia PDF Downloads 244
2896 Comparing of Hypogonadism Frequency between Metabolic Syndrome Men with Normal Men

Authors: Armaghan Moravej Aleali, Seyed Bahman Ghaderian, Homeira Rashidi, Mahmoud Mapar

Abstract:

Background and Objective The metabolic syndrome (MetS) is considered the most important public health threat of the 21st century. This syndrome is characterized by a cluster of cardiovascular risk factors including increased central abdominal obesity, elevated triglycerides, reduced high-density lipoprotein, high blood pressure, increased fasting glucose, and hyperinsulinemia. MetS has been associated with hypogonadism and erectile dysfunction (ED), and MetS may be considered a risk factor for ED. The aim of this study was finding an association between metabolic syndrome and hypogonadism in Khouzestan, Iran. Subjects and Methods: In this study, 60 patients divided into two groups consisted of 30 cases (with metabolic syndrome) and 30 controls. Total and free Serum Testosterone and FBS in all of them were measured. Data was analyzed with SPSS20 program. Results: There was a significant difference between two groups about free Testosterone (P=0.01), FBS (P=0.002) and LH (P=0.03). Conclusion: According to this finding, it is thought the prevalence of hypogonadism in men with metabolic syndrome is more than the general population.

Keywords: metabolic syndrome, fasting blood sugar, hypogonadism, testosterone

Procedia PDF Downloads 401
2895 The Associations between Ankle and Brachial Systolic Blood Pressures with Obesity Parameters

Authors: Matei Tudor Berceanu, Hema Viswambharan, Kirti Kain, Chew Weng Cheng

Abstract:

Background - Obesity parameters, particularly visceral obesity as measured by the waist-to-height ratio (WHtR), correlate with insulin resistance. The metabolic microvascular changes associated with insulin resistance causes increased peripheral arteriolar resistance primarily to the lower limb vessels. We hypothesize that ankle systolic blood pressures (SBPs) are more significantly associated with visceral obesity than brachial SBPs. Methods - 1098 adults enriched in south Asians or Europeans with diabetes (T2DM) were recruited from a primary care practice in West Yorkshire. Their medical histories, including T2DM and cardiovascular disease (CVD) status, were gathered from an electronic database. The brachial, dorsalis pedis, and posterior tibial SBPs were measured using a Doppler machine. Their body mass index (BMI) and WHtR were calculated after measuring their weight, height, and waist circumference. Linear regressions were performed between the 6 SBPs and both obesity parameters, after adjusting for covariates. Results - Generally, the left posterior tibial SBP (P=4.559*10⁻¹⁵) and right posterior tibial SBP (P=1.114* 10⁻¹³ ) are the pressures most significantly associated with the BMI, as well as in south Asians (P < 0.001) and Europeans (P < 0.001) specifically. In South Asians, although the left (P=0.032) and right brachial SBP (P=0.045) were associated to the WHtR, the left posterior tibial SBP (P=0.023) showed the strongest association. Conclusion - Regardless of ethnicity, ankle SBPs are more significantly associated with generalized obesity than brachial SBPs, suggesting their screening potential for screening for early detection of T2DM and CVD. A combination of ankle SBPs with WHtR is proposed in south Asians.

Keywords: ankle blood pressures, body mass index, insulin resistance, waist-to-height-ratio

Procedia PDF Downloads 145
2894 Predicting High-Risk Endometrioid Endometrial Carcinomas Using Protein Markers

Authors: Yuexin Liu, Gordon B. Mills, Russell R. Broaddus, John N. Weinstein

Abstract:

The lethality of endometrioid endometrial cancer (EEC) is primarily attributable to the high-stage diseases. However, there are no available biomarkers that predict EEC patient staging at the time of diagnosis. We aim to develop a predictive scheme to help in this regards. Using reverse-phase protein array expression profiles for 210 EEC cases from The Cancer Genome Atlas (TCGA), we constructed a Protein Scoring of EEC Staging (PSES) scheme for surgical stage prediction. We validated and evaluated its diagnostic potential in an independent cohort of 184 EEC cases obtained at MD Anderson Cancer Center (MDACC) using receiver operating characteristic curve analyses. Kaplan-Meier survival analysis was used to examine the association of PSES score with patient outcome, and Ingenuity pathway analysis was used to identify relevant signaling pathways. Two-sided statistical tests were used. PSES robustly distinguished high- from low-stage tumors in the TCGA cohort (area under the ROC curve [AUC]=0.74; 95% confidence interval [CI], 0.68 to 0.82) and in the validation cohort (AUC=0.67; 95% CI, 0.58 to 0.76). Even among grade 1 or 2 tumors, PSES was significantly higher in high- than in low-stage tumors in both the TCGA (P = 0.005) and MDACC (P = 0.006) cohorts. Patients with positive PSES score had significantly shorter progression-free survival than those with negative PSES in the TCGA (hazard ratio [HR], 2.033; 95% CI, 1.031 to 3.809; P = 0.04) and validation (HR, 3.306; 95% CI, 1.836 to 9.436; P = 0.0007) cohorts. The ErbB signaling pathway was most significantly enriched in the PSES proteins and downregulated in high-stage tumors. PSES may provide clinically useful prediction of high-risk tumors and offer new insights into tumor biology in EEC.

Keywords: endometrial carcinoma, protein, protein scoring of EEC staging (PSES), stage

Procedia PDF Downloads 223
2893 Role of Selenium and Vitamin E in Occupational Exposure to Heavy Metals (Mercury, Lead and Cadmium): Impact of Working in Lamp Factory

Authors: Tarek Elnimr, Rabab El-kelany

Abstract:

Heavy metals are environmental contaminants that may pose long-term health risks. Unfortunately, the consequent implementation of preventive measures was generally delayed, causing important negative effects to the exposed populations. The objective of this study was to determine whether co-consumption of nutritional supplements as selenium and vitamin E would treat the hazardous effects of exposure to mercury, lead and cadmium. 108 workers (60 males and 48 females) were the subject of this study, their ages ranged from 19-63 years, (M = 29.5±10.12). They were working in lamp factory for an average of 0.5-40 years (M= 5.3±8.8). Twenty control subjects matched for age and gender were used for comparison. All workers were subjected to neuropsychiatric evaluation. General Health Questionnaire (GHQ-28) revealed that 44.4% were complaining of anxiety, 52.7% of depression, 41.6% of social dysfunction and 22.2% of somatic symptoms. Cognitive tests revealed that long-term memory was not affected significantly when compared with controls, while short term memory and perceptual ability were affected significantly. Blood metal levels were measured by Inductively Coupled Plasma – optical emission spectrometry(ICP-OES), and revealed that the mean blood mercury, lead and cadmium concentrations before treatment were 1.6 mg/l, 0.39 mg/l and 1.7 µg/l, while they decreased significantly after treatment to 1.2 mg/l, 0.29 mg/l and 1.3 µg/l respectively. Anti-oxidative enzymes (paraoxonase and catalase) and lipid peroxidation product (malondialdehyde) were measured before and after treatment with selenium and vitamin E, and showed significant improvement. It could be concluded that co-consumption of selenium and vitamin E produces significant decrease in mercury, lead and cadmium levels in blood.

Keywords: mercury, lead, cadmium, neuropsychiatric impairment, selenium, vitamin E

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2892 Molecular Modeling a Tool for Postulating the Mechanism of Drug Interaction: Glimepiride Alters the Pharmacokinetics of Sildenafil Citrate in Diabetic Nephropathy Animals

Authors: Alok Shiomurti Tripathi, Ajay Kumar Timiri, Papiya Mitra Mazumder, Anil Chandewar

Abstract:

The present study evaluates the possible drug interaction between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ) induced in diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction by molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg/kg, ip) and confirms it by assessing the blood and urine biochemical parameters on 28th day of its induction. Selected DN animals were used for the drug interaction between GLIM (0.5mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) after 29th and 70th day of protocol. Drug interaction were assessed by evaluating the plasma drug concentration using HPLC-UV and also determine the change in the biochemical parameter in blood and urine. Mechanism of the interaction was postulated by molecular modeling study using Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in the blood and urine biochemical parameter in STZ treated groups. The concentration of SIL increased significantly (p<0.001) in rat plasma when co administered with GLIM after 70th day of protocol. Molecular modelling study revealed few important interactions with rat serum albumin and CYP2C9.GLIM has strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL. Whereas, for CYP2C9, GLIM has strong hydrogen bond with polar contacts and hydrophobic interactions than SIL. Present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals and mechanism has been supported by molecular modeling studies.

Keywords: diabetic nephropathy, glimepiride, sildenafil citrate, pharmacokinetics, homology modeling, schrodinger

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2891 Evaluating the Management of Febrile Infants (Less than 90 Days) Presenting to Tallaght Ed- Completed Audit Cycle

Authors: Amel Osman, Stewart McKenna

Abstract:

Aim: Fever may present as the sole sign of a serious underlying infection in young infants. Febrile Infants aged less than 90 days are at an elevated susceptibility to invasive bacterial infections, thus presenting a challenge in ensuring the appropriate management of these cases. This study aims to ensure strict adherence to NICE guidelines for the management of fever in infants between 0 and 90 days presenting to Tallaght Hospital ED. A comprehensive audit, followed by a re-audit, was conducted to enhance the quality of care delivered to these patients. In accordance with NICE guidelines, all febrile infants should undergo blood tests. Additionally, LP should be performed in all neonates under 28 days, infants displaying signs of illness, and those with WCC below 5 or above 15. Method: A retrospective case review was performed, encompassing all patients aged between 0 to 90 days who presented with fever at Tallaght ED. Data retrieval was conducted from electronic records on two separate occasions, six months apart. The evaluation encompassed the assessment of body temperature as well as both partial and full septic workups. Results: Over the study period, 150 infants presented to the ED with fever in the initial audit, and 120 in the re-audit. In the first study, 81 patients warranted a full septic workup as per NICE, but only 48 received it. Conversely, 40 patients met criteria for a partial septic workup, with 12 undergoing blood tests. In the second study, 73 patients qualified for a full septic workup, of which 52 were completed. Additionally, 27 patients were indicated for a partial workup, with 20 undergoing blood tests. Conclusion: Managing febrile infants under three months of age presenting to Tallaght ED remains a persistent challenge, underscoring the need for continuous educational initiatives to guarantee that these patients receive the requisite assessments and treatments.

Keywords: infants, fever, septic workup, tallaght

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2890 Effect of Intraperitoneal Administration of Ghrelin on Serum Glucose and Insulin Levels in Turkey

Authors: Habib Aghdam Shahryar

Abstract:

The aim of the present study was investigation on the effect of intraperipheral (IP) injection of ghrelin on serum insulin and glucose levels in native turkey. Seventy-two 28 day (d)-old native turkey were assigned into three treatments and four replicate for 40 days experimental rearing period: group 1, intact without any injection, group 2, injected 50 ng ghrelin/kg body weight (BW), and group 3, injected 100 ng ghrelin/kg BW. Intraperitoneal injection of rat ghrelin was conducted on d 28 and before the onset of the experimental rearing period. Blood samples were taken 12 hr after injection and 40 days after injection. The result showed glucose concentrations have been affected by administered ghrelin and significant between groups (P<0.01). Injection of ghrelin at G 100 increased glucose level of serum in 12 hr after injection and 40 days after injection (276.6 and 260.0 mg/dl, respectively). Also, by increasing the dose of injected ghrelin, insulin levels than the control group showed an increase (P < 0.001). This study suggests roles of ghrelin in serum biochemical regulation may show a different effect of ghrelin on blood parameters in avian species.

Keywords: ghrelin injection, insulin, glucose, turkey

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2889 Clinical Efficacy of Localized Salvage Prostate Cancer Reirradiation with Proton Scanning Beam Therapy

Authors: Charles Shang, Salina Ramirez, Stephen Shang, Maria Estrada, Timothy R. Williams

Abstract:

Purpose: Over the past decade, proton therapy utilizing pencil beam scanning has emerged as a preferred treatment modality in radiation oncology, particularly for prostate cancer. This retrospective study aims to assess the clinical and radiobiological efficacy of proton scanning beam therapy in the treatment of localized salvage prostate cancer, following initial radiation therapy with a different modality. Despite the previously delivered high radiation doses, this investigation explores the potential of proton reirradiation in controlling recurrent prostate cancer and detrimental quality of life side effects. Methods and Materials: A retrospective analysis was conducted on 45 cases of locally recurrent prostate cancer that underwent salvage proton reirradiation. Patients were followed for 24.6 ± 13.1 months post-treatment. These patients had experienced an average remission of 8.5 ± 7.9 years after definitive radiotherapy for localized prostate cancer (n=41) or post-prostatectomy (n=4), followed by rising PSA levels. Recurrent disease was confirmed by FDG-PET (n=31), PSMA-PET (n=10), or positive local biopsy (n=4). Gross tumor volume (GTV) was delineated based on PET and MR imaging, with the planning target volume (PTV) expanding to an average of 10.9 cm³. Patients received proton reirradiation using two oblique coplanar beams, delivering total doses ranging from 30.06 to 60.00 GyE in 17–30 fractions. All treatments were administered using the ProBeam Compact system with CT image guidance. The International Prostate Symptom Scores (IPSS) and prostate-specific antigen (PSA) levels were evaluated to assess treatment-related toxicity and tumor control. Results and Discussions: In this cohort (mean age: 76.7 ± 7.3 years), 60% (27/45) of patients showed sustained reductions in PSA levels post-treatment, while 36% (16/45) experienced a PSA decline of more than 0.8 ng/mL. Additionally, 73% (33/45) of patients exhibited an initial PSA reduction, though some showed later PSA increases, indicating the potential presence of undetected metastatic lesions. The median post-retreatment IPSS score was 4, significantly lower than scores reported in other treatment studies. Overall, 69% of patients reported mild urinary symptoms, with 96% (43/45) experiencing mild to moderate symptoms. Three patients experienced grade I or II proctitis, while one patient reported grade III proctitis. These findings suggest that regional organs, including the urethra, bladder, and rectum, demonstrate significant radiobiological recovery from prior radiation exposure, enabling tolerance to additional proton scanning beam therapy. Conclusions: This retrospective analysis of 45 patients with recurrent localized prostate cancer treated with salvage proton reirradiation demonstrates favorable outcomes, with a median follow-up of two years. The post-retreatment IPSS scores were comparable to those reported in follow-up studies of initial radiation therapy treatments, indicating stable or improved urinary symptoms compared to the end of initial treatment. These results highlight the efficacy of proton scanning beam therapy in providing effective salvage treatment while minimizing adverse effects on critical organs. The findings also enhance the understanding of radiobiological responses to reirradiation and support proton therapy as a viable option for patients with recurrent localized prostate cancer following previous definitive radiation therapy.

Keywords: prostate salvage radiotherapy, proton therapy, biological radiation tolerance, radiobiology of organs

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2888 Correlation between Creatinine Level with Erectile Dysfunction among Diabetics in Temerloh Health Clinic

Authors: Mohammad Zainie Bin Hassan

Abstract:

Background: Erectile dysfunction (ED) is a complication commonly seen among men with diabetes which can be assessed based upon International Index of Erectile Function (IIEF-5) questionnaire. Creatinine level is a blood test that indicates kidney functionality. Object: To evaluate the association between ED, determined by the IIEF-5scores and Creatinine level in diabetic men attending Temerloh Health Clinic, Pahang, Malaysia.Hence, to identify raising Creatinine level related with ED or not. Methods: All married diabetic patients will be investigated face to face after consented for answering the IIEF-5 questionnaire. Creatinine level will be taken by using standard method.Patients with no sexual partner, refuse to answer the questionnaire, cancer, stroke, heart disease and language barrier will be excluded.Data obtained from IIEF-5 score and Creatinine level will be analyzed by using Pearson correlation. All statistical value determined by p=0.05. ED will be categorized accordingly to IIEF-5 scores: no ED (22-25), mild (17-21), moderate (12-16), severe (8-11) and very severe (1-7). Results: A total of 450 patients were investigated with 385 patients were included (85.6% respondant rate) and 65 patients were excluded in this study with age range from 29 to 85 years old. 7% had no ED, 28% mild ED, 34% moderate ED, 16% severe ED and 15% had very severe ED. There was a significant negative correlation between Creatinine level and IIEF-5 scores (r=-0.218, p <0.001). This result implicated that poor kidney function which indicated by high Creatinine level associated significantly with erectile dysfunction. 93% had ED with a different range of severity which triggers for appropriate aggressive ED management among diabetics. Conclusion: The high level of Creatinine is associated with erectile dysfunction among diabetics in Temerloh Health Clinic.

Keywords: correlation, creatinine level, erectile dysfunction, ED, diabetes

Procedia PDF Downloads 413
2887 Determining the Frequency of Pneumonia Emerging in COVID-19 Infection

Authors: Zoirov Amirdin Olimovich, Akbarov Elbek Elmurodovich

Abstract:

Introduction: Pneumonia that occurs during COVID-19 infection is common among patients. This research was conducted to determine the frequency of symptoms occurring during pneumonia according to the purpose. Objective and Task: The goal of our research is to develop clinical concepts of pneumonia that occur during COVID-19 infection. Our main task is to analyze the results of blood tests and understand the progression of the disease. Research Materials and Methods: The research was conducted among patients admitted to the Tashkent Medical Academy multi-profile clinic in the department of infectious diseases undergoing stationary treatment with a diagnosis of COVID-19. The analyzed patients had an average age of 46, with a total of 48 patients, 23 of whom were female and 25 were male. Research Results: The research results showed the development of pneumonia within three days in 27 patients after COVID-19 infection. During the observation period, 24 patients (88.8%) recovered completely. The X-ray revealed no signs of pneumonia in those who fully recovered. The remaining three patients showed a persistent form of pneumonia. Conclusion: The conclusion of the research indicates that pneumonia during COVID-19 infection develops in many patients, and 88.8% of patients recover completely without any lingering symptoms.

Keywords: COVID-19, pneumonia, the X-ray, blood, TTA

Procedia PDF Downloads 67
2886 Exploiting the Tumour Microenvironment in Order to Optimise Sonodynamic Therapy for Cancer

Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou

Abstract:

Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.

Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound

Procedia PDF Downloads 143
2885 Multi-Classification Deep Learning Model for Diagnosing Different Chest Diseases

Authors: Bandhan Dey, Muhsina Bintoon Yiasha, Gulam Sulaman Choudhury

Abstract:

Chest disease is one of the most problematic ailments in our regular life. There are many known chest diseases out there. Diagnosing them correctly plays a vital role in the process of treatment. There are many methods available explicitly developed for different chest diseases. But the most common approach for diagnosing these diseases is through X-ray. In this paper, we proposed a multi-classification deep learning model for diagnosing COVID-19, lung cancer, pneumonia, tuberculosis, and atelectasis from chest X-rays. In the present work, we used the transfer learning method for better accuracy and fast training phase. The performance of three architectures is considered: InceptionV3, VGG-16, and VGG-19. We evaluated these deep learning architectures using public digital chest x-ray datasets with six classes (i.e., COVID-19, lung cancer, pneumonia, tuberculosis, atelectasis, and normal). The experiments are conducted on six-classification, and we found that VGG16 outperforms other proposed models with an accuracy of 95%.

Keywords: deep learning, image classification, X-ray images, Tensorflow, Keras, chest diseases, convolutional neural networks, multi-classification

Procedia PDF Downloads 98
2884 Radiofrequency and Near-Infrared Responsive Core-Shell Multifunctional Nanostructures Using Lipid Templates for Cancer Theranostics

Authors: Animesh Pan, Geoffrey D. Bothun

Abstract:

With the development of nanotechnology, research in multifunctional delivery systems has a new pace and dimension. An incipient challenge is to design an all-in-one delivery system that can be used for multiple purposes, including tumor targeting therapy, radio-frequency (RF-), near-infrared (NIR-), light-, or pH-induced controlled release, photothermal therapy (PTT), photodynamic therapy (PDT), and medical diagnosis. In this regard, various inorganic nanoparticles (NPs) are known to show great potential as the 'functional components' because of their fascinating and tunable physicochemical properties and the possibility of multiple theranostic modalities from individual NPs. Magnetic, luminescent, and plasmonic properties are the three most extensively studied and, more importantly biomedically exploitable properties of inorganic NPs. Although successful attempts of combining any two of them above mentioned functionalities have been made, integrating them in one system has remained challenge. Keeping those in mind, controlled designs of complex colloidal nanoparticle system are one of the most significant challenges in nanoscience and nanotechnology. Therefore, systematic and planned studies providing better revelation are demanded. We report a multifunctional delivery platform-based liposome loaded with drug, iron-oxide magnetic nanoparticles (MNPs), and a gold shell on the surface of liposomes, were synthesized using a lipid with polyelectrolyte (layersomes) templating technique. MNPs and the anti-cancer drug doxorubicin (DOX) were co-encapsulated inside liposomes composed by zwitterionic phophatidylcholine and anionic phosphatidylglycerol using reverse phase evaporation (REV) method. The liposomes were coated with positively charge polyelectrolyte (poly-L-lysine) to enrich the interface with gold anion, exposed to a reducing agent to form a gold nanoshell, and then capped with thio-terminated polyethylene glycol (SH-PEG2000). The core-shell nanostructures were characterized by different techniques like; UV-Vis/NIR scanning spectrophotometer, dynamic light scattering (DLS), transmission electron microscope (TEM). This multifunctional system achieves a variety of functions, such as radiofrequency (RF)-triggered release, chemo-hyperthermia, and NIR laser-triggered for photothermal therapy. Herein, we highlight some of the remaining major design challenges in combination with preliminary studies assessing therapeutic objectives. We demonstrate an efficient loading and delivery system to significant cell death of human cancer cells (A549) with therapeutic capabilities. Coupled with RF and NIR excitation to the doxorubicin-loaded core-shell nanostructure helped in securing targeted and controlled drug release to the cancer cells. The present core-shell multifunctional system with their multimodal imaging and therapeutic capabilities would be eminent candidates for cancer theranostics.

Keywords: cancer thernostics, multifunctional nanostructure, photothermal therapy, radiofrequency targeting

Procedia PDF Downloads 133
2883 Expression of ACSS2 Genes in Peripheral Blood Mononuclear Cells of Patients with Alzheimer’s Disease

Authors: Ali Bayram, Burak Uz, Remzi Yiğiter

Abstract:

The impairment of lipid metabolism in the central nervous system has been suggested as a critical factor of Alzheimer’s disease (AD) pathogenesis. Homo sapiens acyl-coenyme A synthetase short-chain family member 2 (ACSS2) gene encodes the enzyme acetyl-Coenzyme A synthetase (AMP forming; AceCS) providing acetyl-coenzyme A (Ac-CoA) for various physiological processes, such as cholesterol and fatty acid synthesis, as well as the citric acid cycle. We investigated ACSS2, transcript variant 1 (ACSS2*1), mRNA levels in the peripheral blood mononuclear cells (PBMC) of patients with AD and compared them with the controls. The study group comprised 50 patients with the diagnosis of AD who have applied to Gaziantep University Faculty of Medicine, and Department of Neurology. 49 healthy individuals without any neurodegenerative disease are included as controls. ACSS2 mRNA expression in PBMC of AD/control patients was 0.495 (95% confidence interval: 0.410-0.598), p= .000000001902). Further studies are needed to better clarify this association.

Keywords: Alzheimer’s disease, ACSS2 Genes, mRNA expression, RT-PCR

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2882 The Breast Surgery Movement: A 50 Year Development of the Surgical Specialty

Authors: Lauren Zammerilla Westcott, Ronald C. Jones, James W. Fleshman

Abstract:

The surgical treatment of breast cancer has rapidly evolved over the past 50 years, progressing from Halsted’s radical mastectomy to a public campaign of surgical options, aesthetic reconstruction, and patient empowerment. This article examines the happenings that led to the transition of breast surgery as a subset of general surgery to its own specialized field. Sparked by the research of Dr. Bernard Fisher and the first National Surgical Adjuvant Breast and Bowel Project trial in 1971, the field of breast surgery underwent significant growth over the next several decades, enabling general surgeons to limit their practices to the breast. High surgical volumes eventually led to the development of the first formal breast surgical oncology fellowship in a large community-based hospital at Baylor University Medical Center in 1982. The establishment of the American Society of Breast Surgeons, as well several landmark clinical trials and public campaign efforts, further contributed to the advancement of breast surgery, making it the specialized field of the current era.

Keywords: breast cancer, breast fellowship, breast surgery, surgical history

Procedia PDF Downloads 141
2881 Modified Lot Quality Assurance Sampling (LQAS) Model for Quality Assessment of Malaria Parasite Microscopy and Rapid Diagnostic Tests in Kano, Nigeria

Authors: F. Sarkinfada, Dabo N. Tukur, Abbas A. Muaz, Adamu A. Yahuza

Abstract:

Appropriate Quality Assurance (QA) of parasite-based diagnosis of malaria to justify Artemisinin-based Combination Therapy (ACT) is essential for Malaria Programmes. In Low and Middle Income Countries (LMIC), resource constrain appears to be a major challenge in implementing the conventional QA system. We designed and implemented a modified LQAS model for QA of malaria parasite (MP) microscopy and RDT in a State Specialist Hospital (SSH) and a University Health Clinic (UHC) in Kano, Nigeria. The capacities of both facilities for MP microscopy and RDT were assessed before implementing a modified LQAS over a period of 3 months. Quality indicators comprising the qualities of blood film and staining, MP positivity rates, concordance rates, error rates (in terms of false positives and false negatives), sensitivity and specificity were monitored and evaluated. Seventy one percent (71%) of the basic requirements for malaria microscopy was available in both facilities, with the absence of certifies microscopists, SOPs and Quality Assurance mechanisms. A daily average of 16 to 32 blood samples were tested with a blood film staining quality of >70% recorded in both facilities. Using microscopy, the MP positivity rates were 50.46% and 19.44% in SSH and UHS respectively, while the MP positivity rates were 45.83% and 22.78% in SSH and UHS when RDT was used. Higher concordance rates of 88.90% and 93.98% were recorded in SSH and UHC respectively using microscopy, while lower rates of 74.07% and 80.58% in SSH and UHC were recorded when RDT was used. In both facilities, error rates were higher when RDT was used than with microscopy. Sensitivity and specificity were higher when microscopy was used (95% and 84% in SSH; 94% in UHC) than when RDT was used (72% and 76% in SSH; 78% and 81% in UHC). It could be feasible to implement an integrated QA model for MP microscopy and RDT using modified LQAS in Malaria Control Programmes in Low and Middle Income Countries that might have resource constrain for parasite-base diagnosis of malaria to justify ACT treatment.

Keywords: malaria, microscopy, quality assurance, RDT

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2880 The Accuracy of an 8-Minute Running Field Test to Estimate Lactate Threshold

Authors: Timothy Quinn, Ronald Croce, Aliaksandr Leuchanka, Justin Walker

Abstract:

Many endurance athletes train at or just below an intensity associated with their lactate threshold (LT) and often the heart rate (HR) that these athletes use for their LT are above their true LT-HR measured in a laboratory. Training above their true LT-HR may lead to overtraining and injury. Few athletes have the capability of measuring their LT in a laboratory and rely on perception to guide them, as accurate field tests to determine LT are limited. Therefore, the purpose of this study was to determine if an 8-minute field test could accurately define the HR associated with LT as measured in the laboratory. On Day 1, fifteen male runners (mean±SD; age, 27.8±4.1 years; height, 177.9±7.1 cm; body mass, 72.3±6.2 kg; body fat, 8.3±3.1%) performed a discontinuous treadmill LT/maximal oxygen consumption (LT/VO2max) test using a portable metabolic gas analyzer (Cosmed K4b2) and a lactate analyzer (Analox GL5). The LT (and associated HR) was determined using the 1/+1 method, where blood lactate increased by 1 mMol•L-1 over baseline followed by an additional 1 mMol•L-1 increase. Days 2 and 3 were randomized, and the athletes performed either an 8-minute run on the treadmill (TM) or on a 160-m indoor track (TR) in an effort to cover as much distance as possible while maintaining a high intensity throughout the entire 8 minutes. VO2, HR, ventilation (VE), and respiratory exchange ratio (RER) were measured using the Cosmed system, and rating of perceived exertion (RPE; 6-20 scale) was recorded every minute. All variables were averaged over the 8 minutes. The total distance covered over the 8 minutes was measured in both conditions. At the completion of the 8-minute runs, blood lactate was measured. Paired sample t-tests and pairwise Pearson correlations were computed to determine the relationship between variables measured in the field tests versus those obtained in the laboratory at LT. An alpha level of <0.05 was required for statistical significance. The HR (mean +SD) during the TM (167+9 bpm) and TR (172+9 bpm) tests were strongly correlated to the HR measured during the laboratory LT (169+11 bpm) test (r=0.68; p<0.03 and r=0.88; p<0.001, respectively). Blood lactate values during the TM and TR tests were not different from each other but were strongly correlated with the laboratory LT (r=0.73; p<0.04 and r=0.66; p<0.05, respectively). VE (Lmin-1) was significantly greater during the TR (134.8+11.4 Lmin-1) as compared to the TM (123.3+16.2 Lmin-1) with moderately strong correlations to the laboratory threshold values (r=0.38; p=0.27 and r=0.58; p=0.06, respectively). VO2 was higher during TR (51.4 mlkg-1min-1) compared to TM (47.4 mlkg-1min-1) with correlations of 0.33 (p=0.35) and 0.48 (p=0.13), respectively to threshold values. Total distance run was significantly greater during the TR (2331.6+180.9 m) as compared to the TM (2177.0+232.6 m), but they were strongly correlated with each other (r=0.82; p<0.002). These results suggest that an 8-minute running field test can accurately predict the HR associated with the LT and may be a simple test that athletes and coaches could implement to aid in training techniques.

Keywords: blood lactate, heart rate, running, training

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2879 Effects of Using Clinical Practice Guidelines for Caring for Patients with Severe Sepsis or Septic Shock on Clinical Outcomes Based on the Sepsis Bundle Protocol at the ICU of Songkhla Hospital Thailand

Authors: Pornthip Seangsanga

Abstract:

Sepsis or septic shock needs urgent care because it is a cause of the high mortality rate if patients do not receive timely treatment. Songkhla Hospital does not have a clear system or clinical practice guidelines for treatment of patients with severe sepsis or septic shock, which contributes to the said problem.To compare clinical outcomes based on the protocol after using the clinical guidelines between the Emergency Room, Intensive Care Unit, and the Ward. This quasi-experimental study was conducted on the population and 50 subjects who were diagnosed with severe sepsis or septic shock from December 2013 to May 2014. The data were collected using a nursing care and referring record form for patients with severe sepsis or septic shock at Songkhla Hospital. The record form had been tested for its validity by three experts, and the IOC was 1.The mortality rate in patients with severe sepsis or septic shock who were moved from the ER to the ICU was significantly lower than that of those patients moved from the Ward to the ICU within 48 hours. This was because patients with severe sepsis or septic shock who were moved from the ER to the ICU received more fluid within the first six hours according to the protocol which helped patients to have adequate tissue perfusion within the first six hours, and that helped improve blood flow to the kidneys, and the patients’ urine was found to be with a higher quantity of 0.5 cc/kg/hr, than those patients who were moved from the Ward to the ICU. This study shows that patients with severe sepsis or septic shock need to be treated immediately. Using the clinical practice guidelines along with timely diagnosis and treatment based on the sepsis bundle in giving sufficient and suitable amount of fluid to help improve blood circulation and blood pressure can clearly prevent or reduce severity of complications.

Keywords: clinical practice guidelines, caring, septic shock, sepsis bundle protocol

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2878 Binding Mechanism of Synthesized 5β-Dihydrocortisol and 5β-Dihydrocortisol Acetate with Human Serum Albumin to Understand Their Role in Breast Cancer

Authors: Monika Kallubai, Shreya Dubey, Rajagopal Subramanyam

Abstract:

Our study is all about the biological interactions of synthesized 5β-dihydrocortisol (Dhc) and 5β-dihydrocortisol acetate (DhcA) molecules with carrier protein Human Serum Albumin (HSA). The cytotoxic study was performed on breast cancer cell line (MCF-7) normal human embryonic kidney cell line (HEK293), the IC50 values for MCF-7 cells were 28 and 25 µM, respectively, whereas no toxicity in terms of cell viability was observed with HEK293 cell line. The further experiment proved that Dhc and DhcA induced 35.6% and 37.7% early apoptotic cells and 2.5%, 2.9% late apoptotic cells respectively. Morphological observation of cell death through TUNEL assay revealed that Dhc and DhcA induced apoptosis in MCF-7 cells. The complexes of HSA–Dhc and HSA–DhcA were observed as static quenching, and the binding constants (K) was 4.7±0.03×104 M-1 and 3.9±0.05×104 M-1, and their binding free energies were found to be -6.4 and -6.16 kcal/mol, respectively. The displacement studies confirmed that lidocaine 1.4±0.05×104 M-1 replaced Dhc, and phenylbutazone 1.5±0.05×104 M-1 replaced by DhcA, which explains domain I and domain II are the binding sites for Dhc and DhcA. Further, CD results revealed that the secondary structure of HSA was altered in the presence of Dhc and DhcA. Furthermore, the atomic force microscopy and transmission electron microscopy showed that the dimensions like height and molecular sizes of the HSA–Dhc and HSA–DhcA complex were larger compared to HSA alone. Detailed analysis through molecular dynamics simulations also supported the greater stability of HSA–Dhc and HSA–DhcA complexes, and root-mean-square-fluctuation interpreted the binding site of Dhc as domain IB and domain IIA for DhcA. This information is valuable for the further development of steroid derivatives with improved pharmacological significance as novel anti-cancer drugs.

Keywords: apoptosis, dihydrocortisol, fluorescence quenching, protein conformations

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2877 ScRNA-Seq RNA Sequencing-Based Program-Polygenic Risk Scores Associated with Pancreatic Cancer Risks in the UK Biobank Cohort

Authors: Yelin Zhao, Xinxiu Li, Martin Smelik, Oleg Sysoev, Firoj Mahmud, Dina Mansour Aly, Mikael Benson

Abstract:

Background: Early diagnosis of pancreatic cancer is clinically challenging due to vague, or no symptoms, and lack of biomarkers. Polygenic risk score (PRS) scores may provide a valuable tool to assess increased or decreased risk of PC. This study aimed to develop such PRS by filtering genetic variants identified by GWAS using transcriptional programs identified by single-cell RNA sequencing (scRNA-seq). Methods: ScRNA-seq data from 24 pancreatic ductal adenocarcinoma (PDAC) tumor samples and 11 normal pancreases were analyzed to identify differentially expressed genes (DEGs) in in tumor and microenvironment cell types compared to healthy tissues. Pathway analysis showed that the DEGs were enriched for hundreds of significant pathways. These were clustered into 40 “programs” based on gene similarity, using the Jaccard index. Published genetic variants associated with PDAC were mapped to each program to generate program PRSs (pPRSs). These pPRSs, along with five previously published PRSs (PGS000083, PGS000725, PGS000663, PGS000159, and PGS002264), were evaluated in a European-origin population from the UK Biobank, consisting of 1,310 PDAC participants and 407,473 non-pancreatic cancer participants. Stepwise Cox regression analysis was performed to determine associations between pPRSs with the development of PC, with adjustments of sex and principal components of genetic ancestry. Results: The PDAC genetic variants were mapped to 23 programs and were used to generate pPRSs for these programs. Four distinct pPRSs (P1, P6, P11, and P16) and two published PRSs (PGS000663 and PGS002264) were significantly associated with an increased risk of developing PC. Among these, P6 exhibited the greatest hazard ratio (adjusted HR[95% CI] = 1.67[1.14-2.45], p = 0.008). In contrast, P10 and P4 were associated with lower risk of developing PC (adjusted HR[95% CI] = 0.58[0.42-0.81], p = 0.001, and adjusted HR[95% CI] = 0.75[0.59-0.96], p = 0.019). By comparison, two of the five published PRS exhibited an association with PDAC onset with HR (PGS000663: adjusted HR[95% CI] = 1.24[1.14-1.35], p < 0.001 and PGS002264: adjusted HR[95% CI] = 1.14[1.07-1.22], p < 0.001). Conclusion: Compared to published PRSs, scRNA-seq-based pPRSs may be used not only to assess increased but also decreased risk of PDAC.

Keywords: cox regression, pancreatic cancer, polygenic risk score, scRNA-seq, UK biobank

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2876 Effect of Different Level of Pomegranate Molasses on Performance, Egg Quality Trait, Serological and Hematological Parameters in Older Laying Hens

Authors: Ismail Bayram, Aamir Iqbal, E. Eren Gultepe, Cangir Uyarlar, Umit Ozcınar, I. Sadi Cetingul

Abstract:

The current study was planned with the objective to explore the potential of pomegranate molasses (PM) on performance, egg quality and blood parameters in older laying hens. A total of 240 Babcock white laying hens (52 weeks old) were divided into 5 groups (n=48) with 8 subgroups having 6 hens in each. Pomegranate molasses was added in the drinking water to experimental groups with 0 %, 0.1%, 0.25 %, 0.5%, and 1%, respectively during one month. In our results, egg weight values were remained the same in all pomegranate molasses supplemented groups except 1% group over control. However, feed consumption, egg production, feed conversion ratio (FCR), egg mass, egg yolk cholesterol, body weights, and water consumption remained unaffected (P > 0.05). During mid-study (15 Days) analyses, egg quality parameters such as Haugh unit, eggshell thickness, albumin index, yolk index, and egg yolk color were remained non-significant (P > 0.05) while after final (30 Days) egg analyses, only egg yolk color had positively (P < 0.05) increased in 0.5% group. Moreover, Haugh unit, eggshell thickness, and albumin index were not significantly (P > 0.05) affected by the supplementation of pomegranate molasses. Regarding serological parameters, pomegranate molasses did not show any positive effect on cholesterol, total protein, LDL, HDL, GGT, AST, ALT, and glucose level. Similarly, pomegranate molasses also showed non-significant (P > 0.05) results on different blood parameters such as HCT, RBC, MCV, MCH, MCHC, PLT, RDWC, MPV except hemoglobin level. Only hemoglobin level was increased in all experimental groups over control showing that pomegranate molasses can be used as an enhancer in animals with low hemoglobin level.

Keywords: pomegranate molasses, laying hen, egg yield, blood parameters

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2875 Exploring the Relationship Between Helicobacter Pylori Infection and the Incidence of Bronchogenic Carcinoma

Authors: Jose R. Garcia, Lexi Frankel, Amalia Ardeljan, Sergio Medina, Ali Yasback, Omar Rashid

Abstract:

Background: Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that affects nearly half of the population worldwide and humans serve as the principal reservoir. Infection rates usually follow an inverse relationship with hygiene practices and are higher in developing countries than developed countries. Incidence varies significantly by geographic area, race, ethnicity, age, and socioeconomic status. H. pylori is primarily associated with conditions of the gastrointestinal tract such as atrophic gastritis and duodenal peptic ulcers. Infection is also associated with an increased risk of carcinogenesis as there is evidence to show that H. pylori infection may lead to gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. It is suggested that H. pylori infection may be considered as a systemic condition, leading to various novel associations with several different neoplasms such as colorectal cancer, pancreatic cancer, and lung cancer, although further research is needed. Emerging evidence suggests that H. pylori infection may offer protective effects against Mycobacterium tuberculosis as a result of non-specific induction of interferon- γ (IFN- γ). Similar methods of enhanced immunity may affect the development of bronchogenic carcinoma due to the antiproliferative, pro-apoptotic and cytostatic functions of IFN- γ. The purpose of this study was to evaluate the correlation between Helicobacter pylori infection and the incidence of bronchogenic carcinoma. Methods: The data was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate the patients infected versus patients not infected with H. pylori using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale for the purpose of academic research. Standard statistical methods were used. Results:-Between January 2010 and December 2019, the query was analyzed and resulted in 163,224 in both the infected and control group, respectively. The two groups were matched by age range and CCI score. The incidence of bronchogenic carcinoma was 1.853% with 3,024 patients in the H. pylori group compared to 4.785% with 7,810 patients in the control group. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.367 (0.353 - 0.383) with a confidence interval of 95%. The two groups were matched by treatment and incidence of cancer, which resulted in a total of 101,739 patients analyzed after this match. The incidence of bronchogenic carcinoma was 1.929% with 1,962 patients in the H. pylori and treatment group compared to 4.618% with 4,698 patients in the control group with treatment. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.403 (0.383 - 0.425) with a confidence interval of 95%.

Keywords: bronchogenic carcinoma, helicobacter pylori, lung cancer, pathogen-associated molecular patterns

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2874 Histological and Ultrastructural Study on the Effect

Authors: Olfat Mohamed Hussien Yousef

Abstract:

Tamoxifen (TM) is a synthetic non-steroidal antiestrogen. It is one of the most effective drugs for treatment of estrogen-dependent cancer by binding to estrogen receptors, suppressing of epithelial proliferation and as a chemotherapeutic agent. Recently, more attention has been paid to the protective effects of natural antioxidants against toxicities induced by anti-cancer drugs involving free radical-mediated oxidative stress and tissue injury. Vitamin C is a potent antioxidant that has the ability to scavenge factors causing free radical formation in animals receiving tamoxifen. The present study aims at pinpointing the TM-induced histopathological and ultrastructural changes in the kidneys and to assess the possible chemoprotective role of vitamin C against such TM-induced microscopic changes. Thirty adult male CD-1 mice, 25-30 g in weight and 3 months old, were divided into three groups. The first group served as control. The second group received the therapeutic dose of TM at daily oral dose of 40 mg/kg body weight for 28 days. The third group received the therapeutic dose of vitamin C at a daily dose of 500 mg/kg body weight simultaneously with the therapeutic dose of TM used in group two for 28 days. Animals were sacrificed and kidney samples were obtained and processed for histological and ultrastructural examination. Histological changes induced by TM included damage of the renal corpuscles including obliteration of the subcapsular space, congestion of the glomerular blood capillaries, segmental mesangial cell proliferation with matrix expansion, capsular adhesions with the glomerular tuft especially at the urinary pole of the corpuscles. Moreover, some proximal and distal tubules suffered various degrees of degeneration in some lining cells. Haemorrhage and inflammatory cell infiltration were also observed in the intertubular spaces. Ultrastructural observations revealed damage of the parietal epithelium of Bowman’s capsule, fusion and destruction of the foot processes of podocytes and great increase of mesangial cells and mesangial matrix. The cells of the proximal convoluted tubules displayed marked destruction of the microvilli constituting the brush borders and degeneration of the mitochondria; besides, abundant lysosomes, numerous vacuoles and pyknotic nuclei were observed. The distal convoluted tubules displayed marked distruction of both the basal infolding and the mitochondria in some areas. Histological and ultrastructural results revealed that treatment of male mice with TM simultaneously with vitamin C led to apparent repair of the injured renal tissue. This might suggest that vitamin C (an antioxidant agent) can minimize the toxic effects of TM (an antiestrogen).

Keywords: tamoxifen, vitamin c, mammalian kidney, histology, ultrastructure

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